Fig. 14.1 Normal whole body 99mTc-bisphosphonate bone scan; anterior view on left, posterior view on right.
Introduction to nuclear medicine
Reticuloendothelial system: bone marrow scintigraphy
Cerebrospinal fluid shunt patency
Meta-iodobenzylguanidine (MIBG) imaging
Somatostatin receptor scintigraphy: SPECT
Radioiodine thyroid cancer imaging
Positron emission tomography (PET)
Somatostatin receptor scintigraphy: 68Ga-DOTA-peptide PET/CT
Prostate-specific membrane antigen: 68Ga-PSMA PET/CT
11C-choline/18F-fluorocholine PET/CT
Radionuclide ventriculography: MUGA scan
Radionuclide first-pass cardiac studies
Lung scan: ventilation/perfusion imaging
Static cortical scintigraphy: dimercaptosuccinic acid imaging
Gastrointestinal bleeding: labelled red cell imaging
Meckel’s scan: ectopic gastric mucosa localization
Splenunculus detection: heat-damaged red cell imaging
Glomerular filtration rate measurement
Nuclear medicine techniques employ a carrier molecule, selected to target the organ/tissue of interest, tagged with a gamma-emitting radioisotope. The labelled drug (radiopharmaceutical) is usually given PO or IV, although it can also be administered interstitially or by inhalation. Its distribution is mapped in vivo using a gamma camera (scintigraphy) or, for non-imaging tests, biological specimens are assayed in vitro using a radiation counter. SPECT uses images collected, whilst rotating a gamma camera (usually multi-headed) around the patient, then reconstructed mathematically to produce 3D images. PET images are obtained from a ring of detectors following administration of a positron-emitting radiopharmaceutical.
Nuclear medicine procedures can detect early physiological responses to disease processes, generally before structural changes have taken place, and thus scintigraphy is often more sensitive than conventional radiology in early disease. Specificity varies depending on the radiopharmaceutical used, and characterization of abnormalities often relies upon pattern recognition within a particular clinical setting. Anatomical detail is poor, compared with conventional radiology, and increasingly single photon emission computed tomography (SPECT) and positron emission tomography (PET) images are co-registered with CT or MRI images using hybrid cameras.
Nuclear medicine procedures are non-invasive and allow the whole body to be imaged during a single examination. Absorbed radiation doses depend on the radiopharmaceutical used but are usually in the same range as diagnostic radiology. Pregnancy is an absolute contraindication to nuclear medicine examinations, except where likely clinical benefit far outweighs potential risk, e.g. lung perfusion imaging. Some radiopharmaceuticals are excreted in breast milk, and additional precautions may be advisable for lactating women.
Diagnostic radiopharmaceuticals are used in tracer quantities and toxicity is negligible. Individual hypersensitivity reactions are rare. The most widely used radionuclide is technetium-99m (99mTc), which can be obtained from an on-site generator, has a half-life of 6h, and is suitable for labelling a wide variety of radiopharmaceuticals.
•Patient identification details.
•Relevant clinical history, including results of other investigations.
•Pregnancy/lactation details where relevant.
•Special needs—visual/hearing/learning difficulties; needle phobia.
•Some scanning beds have a weight limit.
Nuclear medicine investigations supplement the anatomical information obtained from radiology. Bone scintigraphy is sensitive, with changes frequently detected earlier than on plain film, but non-specific. It plays a pivotal role in the staging of patients with malignant disease and in difficult orthopaedic cases. May be restricted to ‘local views’ only, e.g. loose hip prosthesis or ‘whole body imaging’ in metastatic screening. Can include a dynamic phase image at the time of radiopharmaceutical administration, in addition to the delayed bone phase image 2–4h post-injection. Dynamic phase reflects blood flow to the site of interest—useful when there is concern over vascularity, infection, or recent trauma. Helps to differentiate soft tissue from bone pathology, e.g. cellulitis vs osteomyelitis.
The 99mTc-bisphosphonate complex (MDP/medronate, HDP/oxidronate) targets the skeleton with renal excretion of unbound activity. Patients with poor renal function may need delayed imaging to improve the bone:soft tissue ratio (see Fig. 14.1).
•Tumour staging—assess skeletal metastases (see Fig. 14.2).
•Trauma—when radiographs unhelpful.
•Prosthetic loosening, e.g. total hip replacement (THR).
•Paget’s disease to assess extent (monostotic or polyostotic) (see Fig. 14.3).
Should be well hydrated and continent.
Inject 99mTc-bisphosphonate complex IV. For suspected AVN or sepsis, image immediately to assess vascularity. Otherwise, image 2–4h later. Whole body views are required for metastatic screening. Tomography improves anatomical definition and detection of small lesions, e.g. osteoid osteoma, and is particularly useful in back pain. Fusion with CT images is being used increasingly.
•Radiopharmaceutical uptake reflects osteoblastic activity.
•Focal ↑ uptake in sclerotic metastases, trauma, or infection.
•Diffuse ↑ uptake associated with advanced metastases, Paget’s (local), and metabolic bone disease.
•Reduced tracer uptake in acute AVN and lytic bone metastases.
Sensitive, but non-specific. Interpretation relies on pattern recognition in the clinical setting.
Sensitive—detects early changes in bone physiology, often before abnormal plain radiographs, e.g. occult trauma, metastases, and sepsis.
False −ves in multiple myeloma and osteolytic bone metastases.
False +ves: artefacts due to urine contamination.
Fig. 14.1 Normal whole body 99mTc-bisphosphonate bone scan; anterior view on left, posterior view on right.
Largely superseded by MRI. Colloid particles are cleared from the circulating blood pool by reticuloendothelial tissue—larger particles to the liver and spleen, smaller particles to the BM. Abnormal uptake pattern where the BM is replaced, e.g. by tumour infiltration.
•Suspected malignant marrow infiltration.
•Equivocal conventional bone imaging.
None.
•99mTc-nanocolloid injected IV.
•Whole body gamma camera imaging at 30–45min.
Normal marrow distribution in the thoracic cage, spine, pelvis, and proximal long bones. Homogeneous uptake in the liver and spleen.
•Focal or generalized ↓ skeletal uptake indicates marrow replacement or infiltration with marrow displacement to the distal femora and humeri.
•Heterogeneous hepatic uptake is abnormal but non-specific.
Non-invasive. Avoids sampling errors, compared with BM biopsy.
False −ves in early malignancy. Liver and spleen uptake may obscure abnormalities in the mid spine.
Used to study acute and chronic cerebrovascular disease, dementias, and epilepsy, using a neutral lipophilic 99mTc complex hexamethyl-propylene-amine-oxime (exametazime, HMPAO), which crosses the blood–brain barrier and fixes in proportion to regional blood flow, with high accumulation in cortical grey matter, compared with white matter. Images reported with CT/MRI correlation to ensure appropriate interpretation, compared with normal variants of cerebral asymmetry).
•Epilepsy for localization of epileptogenic focus.
Secure venous access under resting conditions. Allow the patient to relax before injection of the radiopharmaceutical. Ensure that the patient can co-operate with the imaging procedure.
•99mTc-HMPAO (exametazime) injected IV in a quiet, darkened room, with the patient’s eyes closed.
•Tomographic brain imaging undertaken immediately and may be repeated 4h later.
Cortical grey matter uptake is proportional to blood flow (see Fig. 14.4a).
•Characteristic patterns of abnormal uptake recognized in different dementias (see Fig. 14.4b) and in cerebrovascular disease.
•↓ uptake at epileptogenic focus on interictal scans—often changing to ↑ uptake on ictal imaging.
Abnormalities on functional imaging should predate structural atrophy on anatomical imaging.
•Tomographic image analysis degraded by movement artefact and asymmetric positioning.
•Data processing is operator-dependent.
Fig. 14.4 99mTc-HMPAO brain imaging. Trans-axial tomographic slices: (a) normal and (b) dementia. (
Colour plate 6.)
Kapucu OL, Nobili F, Varrone A, et al. EANM procedure guideline for brain perfusion SPECT using 99mTc-labelled radiopharmaceuticals, version 2. Eur J Nucl Med Mol Imaging 2009; 36: 2093–102.
Reflects the role of the dopaminergic system in movement disorders, e.g. Parkinsonian syndromes, essential tremor. 123I-ioflupane is a cocaine analogue, which binds to the dopamine transporter on the pre-synaptic nerve terminal. Post-synaptic receptor imaging agents are necessary to differentiate among the various Parkinsonian syndromes (not routinely available).
•Movement disorders: distinguishes Parkinson’s syndrome (PkS) from benign essential tremor.
•Block the thyroid—potassium iodate/iodide.
•Multiple potential drug interactions—stop:
123I-labelled radiotracer, e.g. ioflupane, injected IV. Tomographic gamma camera imaging 3–6h later.
Intense, symmetric uptake in basal ganglia receptors—striatum, caudate, and putamen (see Fig. 14.5a).
↓ basal ganglia uptake in PkS (see Fig. 14.5b).
Sensitive and specific for PkS, differentiating PkS from essential tremor. No other imaging technique currently available to demonstrate receptor status.
Drug interactions ( Patient preparation above).
Fig. 14.5 123I-ioflupane brain transporter imaging: (a) normal dopamine transporters and (b) in Parkinson’s disease. ( Colour plate 7.)
Darcourt J, Booij J, Tatsch K, et al. EANM procedure guidelines for brain neurotransmission SPECT using 123I-labelled dopamine transporter ligands, version 2. Eur J Nucl Med Mol Imaging 2010; 37: 443–50.
Ventricular shunts are routinely used to manage hydrocephalus. Symptoms of shunt obstruction may be non-specific and do not indicate the level of obstruction. Nuclear medicine offers a straightforward means of determining shunt patency.
Suspected ventriculoperitoneal shunt obstruction.
None.
Inject 111In-DTPA into the shunt reservoir using a strict aseptic technique. Image the head and abdomen immediately and 30–60min post-injection. (99mTc-DTPA not recommended because difficult to ensure apyrogenicity.)
Normally, rapid reservoir emptying and shunt visualization within 2–3min of injection. Free activity within the abdominal cavity by 30min (see Fig. 14.6).
Delayed clearance implies obstruction—level usually at reservoir/proximal shunt or due to intra-abdominal kinking.
Sensitive, simple, rapid results.
Infection risk.
Fig. 14.6 Patent ventriculoperitoneal shunt showing reservoir, shunt, and free activity within the peritoneal cavity.
Used to investigate thyrotoxicosis and thyroid ectopia. Thyroid mass or suspected malignancy should be investigated by US/CT and FNA cytology. Imaging is undertaken using 99mTc-pertechnetate, which is trapped by the thyroid by the same transporter mechanism as iodine but, unlike iodine, is not organified. 123I is more sensitive and specific for the investigation of congenital hypothyroidism.
•Characterization of thyrotoxicosis—diffuse toxic goitre (Graves’ disease), toxic multinodular goitre (Plummer’s disease).
Levothyroxine and iodine-rich preparations (e.g. iodine supplements, contrast media, amiodarone) will block tracer uptake by the thyroid for up to 9 months. T4 should be withdrawn for 4–6 weeks, T3 for 2 weeks. Antithyroid drugs can be continued.
Inject 99mTc-pertechnetate IV. Image after 15–30min. Include anterior thorax views if retrosternal extension is suspected. Neck palpation essential to assess function in discrete thyroid nodules. 123I may be administered either PO or IV. Imaging is carried out at 2h.
•Uptake reflects function of the thyroid iodine trap (sodium iodide symporter).
•Diffuse ↑ uptake in Graves’ disease (see Fig. 14.7a).
•Heterogeneous uptake with suppressed background activity indicates toxic multinodular change (see Fig. 14.7b).
•Solitary autonomous nodules show intense ↑ uptake, with complete suppression of the remainder of the gland (see Fig. 14.7c).
•Reduced tracer uptake in non-functioning nodules (see Fig. 14.7d).
•Acute thyroiditis is characterized by absent tracer uptake (see Fig. 14.7e).
Sensitive and specific for hyperthyroidism.
Simple, cheap, and non-invasive. Essential to planning therapy in hyperthyroidism.
Anatomical definition inferior to US, CT, etc. Superseded by US-guided FNA for diagnosis of thyroid mass lesions.
Fig. 14.7 Thyroid scintigraphy: (a) in Graves’ disease (toxic diffuse hyperplasia) and (b) in toxic multinodular goitre, (c) toxic autonomous nodule (arrow), (d) non-functioning (cold nodule; arrow), and (e) thyroiditis (arrow).
Hyperparathyroidism may be 1° (i.e. functioning adenoma), 2° (where there is hypocalcaemia from chronic lowering of serum Ca2+, e.g. renal insufficiency), or tertiary (i.e. hypersecretion of PTH in the presence of either normal or elevated levels of Ca2+). Nuclear medicine is of value in localizing parathyroid adenomas, particularly following previous surgery.
Localization of parathyroid adenoma in proven hyperparathyroidism.
Withdraw levothyroxine or iodine-containing compounds (cf. thyroid imaging).
Three different techniques are available.
•99mTc-sestamibi IV early (15 min) and delayed (2–3 h) images or
•123I-iodide IV followed by 99mTc-sestamibi, or
•99mTc-pertechnetate followed by 201Tl-thallous chloride.
Image the anterior neck and mediastinum after each administration.
Normal thyroid concentrates 123I, 99mTc-pertechnetate, 99mTc-sestamibi (initially), and 210Tl, whereas parathyroid only concentrates 99mTc-sestamibi and 201Tl.
Computer-assisted image subtraction [(thyroid + parathyroid) − thyroid] identifies abnormal parathyroid tissue.
Parathyroid adenoma shown as hyperfunctioning nodule(s) (see Figs 14.8–14.10.)
Good when other imaging fails, particularly ectopic adenomas and after unsuccessful neck exploration. Hybrid SPECT/CT images particularly helpful to surgeons.
Multinodular thyroid prevents subtraction analysis in smaller adenomas and hyperplastic glands and thyroid nodules. Many surgeons still prefer intra-operative blue dye.
False −ves in smaller adenomas and hyperplastic glands.
False +ves in thryoid nodules.
Fig. 14.8 Normal 99mTc-sestamibi dual-phase parathyroid scan; 5min image on left, 4h image on right.
Fig. 14.9 99mTc-sestamibi (dual-phase). Parathyroid adenoma at left lower lobe of the thyroid (arrow) evident on delayed image.
Fig. 14.10 Parathyroid scintigraphy showing images obtained with both (a) 123I-iodide, (b) 99mTc-sestamibi, and (c) subtracted image showing a parathryoid adenoma.
Hindié E, Ugur O, Fuster D, et al. 2009 EANM parathyroid guidelines. Eur J Nucl Med Mol Imaging 2009; 36: 1201–16.
Neuroendocrine tumours (NETs) are rare. Symptoms reflect hormone hypersecretion, but intermittent secretory patterns can result in false −ve screening tests, e.g. 24h urine collections. MIBG (iobenguane) is concentrated by adrenergic tissue via the noradrenaline reuptake mechanism. Virtually all phaeochromocytomas and neuroblastomas will be demonstrated using 123I-MIBG scintigraphy. The sensitivity for other NETs is variable. High-dose 131I-MIBG therapy is a useful treatment for MIBG +ve NETs.
•Localization, staging, and response monitoring of neuroectodermal tumours.
•Phaeochromocytoma (imaging investigation of choice).
•Multiple known and theoretical drug interactions: Stop for >48h:
•Antidepressants—tricyclics, tetracyclics, MAOIs, serotonin reuptake inhibitors.
•Labetalol (no interaction with any other α- or β-blocker or antihypertensive).
•Sympathomimetics—including over-the-counter nasal decongestants.
•Block the thyroid: potassium iodate/iodide; perchlorate.
Inject 123I-MIBG slowly IV with BP monitoring. Image the posterior abdomen at 5min to identify renal outlines, then whole body imaging at 18–24h. Tomographic imaging may improve tumour localization—not always required.
Physiological uptake at 24h in the salivary glands, myocardium, liver, and normal adrenals, with gut and renal excretion.
•Intense ↑ uptake in phaeochromocytomas, with suppressed activity in the contralateral and normal adrenal, and myocardium. Whole body imaging identifies extra-adrenal and metastatic disease (see Fig. 14.11).
•Diffuse BM uptake common in stage IV neuroblastoma.
Sensitive, non-invasive tumour localization preoperatively excludes multi-focal and extra-adrenal tumours. Non-invasive treatment response monitoring in neuroblastoma—avoids sampling errors, compared with BM biopsy.
Drug interactions causing false −ve results. Dilated renal pelvis sometimes confused with tumour uptake. Check with 5min renal image if in doubt.
Fig. 14.11 123I-MIBG whole body scan. 123I-MIBG positive left adrenal mass (phaeochromocytoma). Excludes multi-focal, ectopic, and malignant tumour.
Somatostatin receptor (SSR) imaging identifies NETs, including gastroenteropancreatic tumours, e.g. carcinoids, gastrinomas, insulinomas. Many other common neoplasms also express surface SSRs. Somatostatin analogues, e.g. octreotide, bind to cell surface SSRs. Radiolabelled SSR analogues demonstrate receptor +ve disease. Sub-centimetre (i.e. below the limits of cross-sectional radiology) hyperfunctioning 1° tumours can be detected. High-dose radiolabelled SSR therapy is used to treat multi-site disease.
Localize and stage NETs, e.g. carcinoid, insulinoma, gastrinoma, phaeochromocytoma, and medullary thyroid cancer.
None. Prophylactic laxatives at time of radiopharmaceutical administration accelerate gut clearance and improve image quality.
Inject 111In-pentetreotide or 99mTc hynic-octreotide (SSR analogues) IV. Whole body gamma camera imaging at 4 and 24h (± 48h), with SPECT if necessary.
Normal uptake in the thyroid, liver, spleen, kidneys, and RES, with gut and renal excretion.
↑ uptake in tumours expressing surface SSRs. SPECT improves detection of small pancreatic and intra-hepatic tumours (see Fig. 14.12).
Tumour uptake predicts symptom response to somatostatin analogue therapy. Image co-registration with CT or MRI improves localization of occult pancreatic NETs.
Interpretation often hindered by gut excretion.
Fig. 14.12 Whole body 111In-octreotide scan in a patient with a neuroendocrine tumour showing somatostatin receptor positive hepatic and extra-hepatic metastases.
Bombardieri E, Ambrosini V, Aktolun C, et al. 111In-pentetreotide scintigraphy: procedure guidelines for tumour imaging. Eur J Nucl Med Mol Imaging 2010; 37: 1441–8.
The treatment for thyroid carcinoma is total thyroidectomy with lymph node dissection, depending on tumour stage. Radioactive iodine is administered post-operatively to ablate the thyroid remnant. Tg can then be used as a tumour marker—Tg is undetectable in the absence of functioning thyroid tissue. Rising Tg following 131I ablation indicates recurrence. If Tg rises, a diagnostic 131I imaging study localizes the site of relapse and assesses the feasibility of further radioiodine therapy. The sensitivity of imaging is ↑ by recombinant TSH stimulation.
Routine differentiated follicular thyroid cancer follow-up, after surgery and 131I thyroid remnant ablation.
Need high TSH drive to stimulate 131I uptake—stop T3/T4 replacement for a minimum of 2 (T3) or 4-6 weeks (T4), or give recombinant TSH. Avoid cold iodine administration, IV contrast media, and amiodarone (cf. thyroid imaging).
Give 131I sodium iodide PO/IV. Obtain blood samples for Tg and TSH at the time of 131I administration. Whole body gamma camera imaging 2–5 days later.
Physiological uptake in salivary glands. Occasional stomach and GI retention. Renal excretion.
Abnormal uptake indicates functioning thyroid metastasis. Anatomical markers improve localization (see Fig. 14.13a and b).
Detects residual tumour and identifies patients likely to benefit from 131I therapy.
False −ve without significant TSH drive—aim for TSH >50mU/L; undifferentiated and papillary tumours may be 131I −ve.
Fig. 14.13 Anterior whole body 131I image showing (a) local tumour recurrence in the thyroid bed and physiological activity in the bowel and (b) local recurrence in the thyroid bed with lung, mediastinal nodal, and skeletal metastases.
Regional lymph node dissection is performed for cancer staging to determine the need for adjuvant therapy. Lymphatic drainage can be demonstrated by radiolabelled colloid imaging, which identifies the first or ‘sentinel’ draining node. Staging based on the excision and histological examination of this node for evidence of metastasis is as reliable as that obtained from block dissection and avoids the morbidity of extended lymph node dissection.
Preoperative assessment in breast cancer and melanoma. May have applications in head and neck, vulval, and penile cancer staging.
None. Usually undertaken within 24h of planned surgery.
Intradermal, subcutaneous, or intratumoural injection of 99mTc-labelled nanocolloid. Gamma camera imaging of draining lymph nodes to identify sentinel node. Where surgery is undertaken within 24h, an intra-operative gamma probe can be used to identify the sentinel node for staging excision biopsy.
Sentinel node usually identifiable 15min to 2h post-injection, depending on the 1° tumour location and injection technique used.
The sentinel node is the first lymph node identified on gamma imaging or the node with the highest radioactive count rate using the gamma probe (see Fig. 14.14a and b).
Accurate sentinel node identification avoids block node dissection where this is undertaken solely for tumour staging.
May fail if local lymphatic channels have been disrupted by previous surgery.
Fig. 14.14 99mTc-nanocolloid sentinel node study. (a) Breast cancer: left breast injection and sentinel lymph node in left axilla (arrow). (b) Melanoma left thigh: left thigh injection (not shown) and sentinel lymph node in left groin (arrow).
Procedure guidelines for several types of cancer are available at: 
http://www.eanm.org.
Breast cancer diagnosis relies on accurate localization (US ± mammography) and tissue biopsy (FNA) or core biopsy. Where mammography is non-diagnostic, MRI, CT, or 18F-FDG PET/CT are useful. Nuclear medicine scintimammography is as sensitive as, but more specific than, MRI and mammography in palpable lesions.
Investigation of suspicious breast lesions, in difficult-to-interpret mammograms, e.g. dense or lumpy breast tissue, calcification, breast implants, previous surgery.
None.
99mTc-sestamibi administered IV ideally into the contralateral foot, with early (5–10min) imaging post-injection. Patient is imaged prone, with the breast fully dependent, with prone and lateral views of each breast, to include the axillae.
Normal distribution of 99mTc-sestamibi is to the myocardium, the liver, and occasionally the thyroid.
Focal accumulation in the breast and/or axilla implies the presence of a tumour. Findings should be interpreted in conjunction with other tests.
Can demonstrate multi-focal, multicentric disease, and both ipsilateral and contralateral axillary spread. May be used to identify the most suitable site for guided biopsy.
Not reliable in small (<1cm) lesions; extravasation of injection in upper limbs may result in false +ve axillary uptake.
Poor injection technique will lead to errors in analysis. The camera and supporting software require high count rate capability, and the technique requires expertise in data analysis to ensure reliable, reproducible results. Close liaison with the referring clinician is essential to maximize the value of the investigation.
Buscombe J, Hill J, Parbhoo S.Scintimammography: A Guide to Good Practice. Birmingham: Gibbs Associates Ltd, 1998.
Taillefer R. Clinical applications of 99mTc-sestamibi scintimammography. Semin Nucl Med 2005; 35: 100–15.
PET has expanded rapidly over the last 20 years. Tomographic PET images are acquired using a dedicated PET scanner after administration of positron-emitting radiopharmaceuticals. Spatial resolution (~5mm) is significantly superior to conventional nuclear medicine imaging.
PET uses biologically important molecules such as radiolabelled water, ammonia, amino acids, or glucose derivatives—the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) being used for most clinical PET studies, particularly in oncology. Malignant cells have both a higher glycolytic rate and over-expression of membrane glucose transporters, leading to high 18F-FDG uptake, compared to normal tissues. 18F-FDG is trapped within metabolically active cells, so that abnormalities are detected by metabolic differences, rather than anatomical size, i.e. inherently more sensitive than structure-based imaging.
The main indications for PET imaging are in oncology where 18F-FDG PET is used for diagnosis, staging, and monitoring treatment response. Low-grade uptake occurs in granulomatous disease, inflammation, and sepsis.
PET allows radioactive concentrations within tissues to be measured accurately, so that physiological processes can be expressed in absolute units. The standardized uptake value (SUV) measures the concentration of tracer within a tumour, compared to the injected activity, normalized to body weight. Serial SUV measurements allow 18F-FDG uptake to be followed as a marker of treatment response and may be of prognostic value.
Other major applications include nuclear cardiology where patterns of myocardial 18F-FDG uptake are used to detect myocardial hibernation. In neurosciences, PET remains a largely research tool for the investigation of movement disorders, dementia, and degenerative disease.
Other oncological tracers that are available for clinical use include 11C-methionine, measuring tumour amino acid transport and protein synthesis and H215O water for blood flow measurements. 68Ga-labelled somatostatin peptides are used to image NETs. Future developments will include labelled thymidine analogues (e.g. 18F-FLT) to measure proliferation, hypoxia markers, and tracers capable of detecting apoptosis and angiogenesis.
The main limitation of PET imaging in oncology is limited anatomical definition. To improve attenuation correction and tomographic localization, PET imaging is usually combined with CT (or MRI). The combination of functional and anatomical data in fused images significantly improves the sensitivity and specificity of imaging.
•Tumour diagnosis: solitary pulmonary nodule characterization, location of carcinoma of unknown 1° origin.
•Tumour staging: non-SCLC; lymphoma; oesophageal cancer; colorectal cancer; head and neck cancer; melanoma.
•Response assessment/relapse detection: as above.
•Cellular 18F-FDG uptake is glucose-dependent.
•Non-diabetic patients—6h fast.
•Aim for blood glucose <7mmol/L.
•Insulin-dependent diabetic patients—allow a normal diet and insulin.
•Avoid hyperglycaemia—use a sliding scale if necessary or defer the investigation.
•Patients should be rested: to avoid skeletal muscle uptake.
•Diazepam administration: 5mg PO reduces physiological brown fat uptake in young patients.
•Patients with head and neck cancer should be silent during injection and until completion of imaging to prevent vocal cord uptake.
•18F-FDG injected IV supine in restful surroundings.
•Whole body or half-body (base of skull to proximal femora) imaging undertaken 60–90min post-injection.
The normal distribution of 18F-FDG is to the brain and myocardium, with GI and renal excretion (see Fig. 14.15).
Abnormal uptake should be correlated with cross-sectional imaging for precise anatomical localization (see Figs 14.16 and 14.17). SUV ( pp. 894–897) measurement is helpful in serial studies.
•Discriminates between viable and necrotic/scar tissue where a residual mass may persist on anatomical imaging post-therapy (see Figs 14.18 and 14.19).
•Non-invasive, whole body 3D imaging.
•Sensitivity lower in more indolent tumours—lung carcinoid, alveolar cell carcinoma, NETs, depending on proliferative index, and occasionally in pancreatic tumours.
•Limited availability—specialist centres only.
Fig. 14.17 18F-FDG PET scan—trans-axial views showing CT (top left) correlation with PET (top right). The image fusion is shown (bottom left). ( Colour plate 8.)
Fig. 14.18 18F-FDG PET scan—non-Hodgkin’s lymphoma. Whole body coronal view of patient pre-treatment showing extensive FDG-avid adenopathy.
Fig. 14.19 18F-FDG PET scan—non-Hodgkin’s lymphoma. Post-treatment showing complete metabolic response.
SSR imaging identifies NETs, including gastroenteropancreatic tumours, e.g. carcinoids, gastrinomas, insulinomas. Many other common neoplasms also express surface SSRs. Somatostatin analogues, e.g. octreotide, bind to cell surface SSRs. Radiolabelled SSR analogues demonstrate receptor +ve disease. High-dose radiolabelled SSR therapy is used to treat multi-site disease. Currently, given its high accuracy, compared with conventional SPECT imaging techniques, 68Ga-DOTA-peptide PET/CT is considered to be the first-line diagnostic imaging technique of choice for high SSR-expressing tumours.
Localize and stage NETs, e.g. carcinoid, insulinoma, gastrinoma, phaeochromocytoma, and medullary thyroid cancer.
Best option is to perform the study after discontinuing short-acting octreotide for 12–24h and perform imaging in the week before the next dose of long-acting octreotide.
Inject 68Ga-labelled SSR analogue (DOTA-TATE/DOTA-NOC) IV. Whole body (vertex to mid thigh) PET/CT imaging SSR PET/CT is performed 45–60min after radiotracer injection.
Normal uptake in the spleen, adrenal glands, kidneys, and pituitary gland. Moderately intense uptake is often seen in the liver, salivary glands, and thyroid gland (see Fig. 14.20a).
↑ uptake in tumours expressing surface SSRs (see Fig. 14.20b).
Short half-life of 68min (compared with 2.8 days for 111In); lower radiation dose to the patient; imaging performed 45–60min after radiotracer injection; more accurate than conventional imaging; and allows identification of additional sites of disease and helps identify patients who are suitable for radiopeptide therapy (e.g. 177Lu-DOTA-TATE).
False −ve: octreotide therapy or the endogenous production of somatostatin by the tumour may interfere with tumour detection. False +ve: prominent pancreatic uncinate process uptake, benign meningioma inflammation, osteoblastic activity (degenerative bone disease, fracture, vertebral haemangioma), splenunculi or splenosis, etc.
Fig. 14.20 (a) Normal 68Ga-DOTA-TATE scan; (b) abnormal 68Ga-DOTA-TATE scan showing liver metastases.
Virgolini I, Ambrosini V, Bomanji JB, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE. Eur J Nucl Med Mol Imaging 2010; 37: 2004–10.
Prostate-specific membrane antigen (PSMA) is a cell surface protein with high expression in prostate cancer cells, and over-expression enables targeting of prostate cancer metastases using 68Ga-labelled PSMA ligands for PET/CT imaging.
High-risk prostate cancer prior to radical prostatectomy, patients with rising PSA levels after radical prostatectomy, and diagnosis of recurrent prostate cancer.
None.
68Ga-PSMA is injected IV and PET/CT performed 60min post-injection.
Physiological uptake in kidneys and salivary glands. ↑ uptake in prostate cancer cells expressing PSMA (see Fig. 14.21a).
↑ tracer uptake in tumours expressing PSMA (prostate and extra-prostatic) (see Fig. 14.21b).
Superior to choline tracers in detecting prostate cancer cells and recurrent disease at low PSA levels.
False −ve: limited detection of micrometastases. False +ve: PSMA is also expressed in tumour-associated neovasculature of most solid tumours.
Fig. 14.21 (a) Normal 68Ga-PSMA scan; (b) abnormal scan with multiple osseous and extra-osseous metastases.
Maurer T, Gschwend JE, Rauscher I, et al. Diagnostic efficacy of 68Gallium-PSMA positron emission tomography compared to conventional imaging in lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 2016; 195: 1436–43.
Following radical prostatectomy for treatment of prostate cancer, recurrent disease is suspected if there is rising PSA.18F-choline PET/CT is often used in restaging of patients with prostate cancer (11C-choline or 11C-acetate PET can also be used where available).
Prostate cancer patients with rising PSA levels after radical prostatectomy and in patients with recurrent prostate cancer.
Fasting for 6h recommended to minimize impact of dietary choline. Patient should be well hydrated.
11C-choline (half-life 20min) is injected IV and PET images acquired over 0–15min. 18F-choline (half-life 110min) is injected IV and scan is performed at 1h.
Physiological uptake in the liver, pancreas, spleen, salivary and lacrimal glands, urinary tract, and less commonly in BM and intestines (see Fig.14.22a).
↑ tracer uptake in recurrent prostate cancer and metastases (see Fig.14.22b).
High specificity in lymph node staging, high sensitivity in recurrent disease, and often helps in treatment planning.
(a) Limited accuracy for the staging of the 1° tumour; (b) often unable to differentiate prostate cancer from benign prostate hyperplasia, chronic prostatitis, and high-grade intraepithelial neoplasia; and (c) high background signal frequently hampers lesion detection.
Schillaci O, Calabria F, Tavolozza M, et al. 18F-choline PET/CT physiological distribution and pitfalls in image interpretation: experience in 80 patients with prostate cancer. Nucl Med Commun 2010; 31: 39–45.
18F-fluoride is a highly sensitive bone-seeking PET tracer used for detection of skeletal pathology. In general, the tracer uptake mechanism is similar to conventional SPECT tracer. The CT component of the PET/CT study allows localization, characterization, and differentiation of skeletal metastases from benign lesions.
Similar to99mTc-MDP bone scan:
•Tumour staging—assess skeletal metastases.
Patients should be (a) well hydrated and (b) instructed to empty their bladder immediately before imaging.
18F-fluoride is injected IV. The adult activity is 185–370MBq. Paediatric activity should be weight-based (2.22MBq/kg).
•Radiopharmaceutical uptake reflects osteoblastic activity (see Fig. 14.23a).
•Focal ↑ uptake in sclerotic metastases (see Fig. 14.23b), trauma, or infection.
•Diffuse ↑ uptake associated with advanced metastases, Paget’s, and metabolic bone disease.
Highly sensitive, but non-specific. Interpretation relies on pattern recognition in the clinical setting. The CT component of PET/CT, even when performed primarily for attenuation correction and anatomic registration, also provides diagnostic information.
Sensitive—detects early changes in bone physiology, often before abnormal plain radiographs, e.g. occult trauma, metastases, and sepsis.
Fig. 14.23 (a) Normal 18F-fluoride scan; (b) abnormal scan with multiple skeletal metastases in the spine.
Segall G, Delbeke D, Stabin MG, et al. SNM practice guideline for sodium 18F-fluoride PET/CT bone scans 1.0. J Nucl Med 2010; 51: 1813–20.
MPI reflects regional blood flow during stress (↑ demand) and at rest, providing prognostically significant information that, both in isolation and in conjunction with coronary angiography, can be used to optimize patient management. Originally performed using 201Tl-thallous chloride, but now based on 99mTc-labelled tracers—sestamibi (methoxy-isobutylisonitrile) or tetrofosmin. Exercise or pharmacological stress are used to challenge the coronary artery reserve. Exercise is performed by treadmill or bicycle, whilst pharmacological stressors are either adenosine/dipyridamole infusion, which ↑ coronary artery blood flow by vasodilatation, or dobutamine infusion with both inotropic and chronotropic activity. Can also be performed using PET/CT with 82Rb-rubidium chloride or 13N-ammonia as tracer.
•When conventional stress testing fails, e.g. bundle branch block.
•Left ventricular hypertrophy.
•Recurrent chest pain post-intervention. Good prognostic indicator.
•Assess functional significance of known stenoses.
•Identify critical vascular territory for intervention.
•Stop β-blockers 24h prior to stress study.
•Sometimes helpful to withdraw all anti-anginal medication.
•Assess the optimal stress technique for individual patients, i.e. exercise or pharmacological.
•Treadmill or bicycle exercise to >85% of maximum predicted heart rate or adenosine 140µg/kg/min IV infusion for 6min—sometimes with submaximal exercise or dobutamine 5–40µg/kg/min in 5µg/kg/min increments over 16min.
•Inject the radiopharmaceutical (201Tl-thallous chloride, 99mTc-sestamibi, or 99mTc-tetrofosmin) at peak stress.
•Tomographic imaging immediately (201Tl) or 15–60min post-injection (99mTc compounds). Images generally acquired with ECG gating.
•Second 99mTc radiopharmaceutical injection under resting conditions.
•Tomographic imaging as before.
•With 201Tl, second injection not necessary, since tracer redistributes into ischaemic areas over 4h, but top-up dose sometimes given.
Myocardial uptake reflects radiopharmaceutical delivery and myocyte function (see Fig. 14.24).
Infarction causes matched perfusion defects during stress and rest. Inducible ischaemia creates a perfusion defect at stress, which reperfuses at rest = reversible ischaemia (see Fig. 14.25). The severity, extent, and number of reversible defects are prognostically significant. A normal MPI study implies risk of an adverse cardiac event of <0.5% per annum.
Non-invasive; relatively inexpensive, compared with angiography.
Less sensitive in multiple small-vessel coronary disease, e.g. DM. Sensitivity depends on stress test quality.
Fig. 14.24 Normal myocardial perfusion scan. ( Colour plate 9.)
Fig. 14.25 Myocardial perfusion scan: (a) in fixed perfusion loss (anterolateral infarction) and (b) in inferior stress-induced (reversible) ischaemia. ( Colour plate 10.)
Marcassa C, Bar JJ, Bengel F, et al. Clinical value, cost-effectiveness, and safety of myocardial perfusion scintigraphy: a position statement. Eur Heart J 2008; 29: 557–63.
Verberne HJ, Acampa W, Anagnostopoulos C, et al. EANM procedural guidelines for radionuclide myocardial perfusion imaging with SPECT and SPECT/CT: 2015 revision. Eur J Nucl Med Mol Imaging 2015; 42: 1929–40.
Increasingly replaced by TTE, TOE, and contrast ventriculography at time of cardiac catheterization. Multigated radionuclide angiography (MUGA) scans are less operator-dependent than either TTE or TOE, which is important in serial assessment. The cardiac blood pool is imaged dynamically after injection of radiolabelled RBCs. Wall motion, synchronicity of ventricular contraction, and EF are measured (see Fig. 14.26). The estimated EF unreliable in presence of dysrhythmias—acquisition requires a relatively regular heart rate.
•LVEF measurement, e.g. unechogenic patients (see Fig. 14.27).
•Monitor anthracycline cardiotoxicity.
None.
Radiolabel red cells (in vivo or in vitro) using 99mTc-pertechnetate. Image the patient supine in anterior and left anterior oblique projections. Camera acquisition gated to cardiac cycle. Imaging may be combined with low-impact exercise/pharmacological stress to assess cardiac reserve.
Visual image of 300–400 summated cardiac cycles. Computer-generated images used to assess regional wall motion and synchronous contraction (see Fig. 14.27). Computer-generated EF calculation. Normal EF 60–70%, ↓ with age.
To monitor treatment response in cardiac failure, cardiomyopathy.
Good for serial measurements during anthracycline chemotherapy. Reliable in unechogenic subjects.
Moderately high radiation dose: echocardiography preferable in most patients.
Cardiac dysrhythmias interfere with gating, e.g. AF.
Fig. 14.27 MUGA scan showing (a) LV regions of interest at end-diastole and (b) end-systole for EF calculation; (c) amplitude image showing relative anteroseptal hypokinesis, but (d) synchronous LV contraction. ( Colour plate 11.)
Hesse B, Lindhardt TB, Acampa W, et al. EANM/ESC guidelines for radionuclide imaging of cardiac function. Eur J Nucl Med Mol Imaging 2008; 35: 851–85.
Nuclear medicine can assess simple shunts, e.g. left-to-right shunts (ventricular and atrial septal defects), but has no place in bidirectional shunting or multiple sources of pulmonary blood flow (e.g. patent ductus arteriosus). First-pass studies quantify shunt severity both pre- and post-surgical correction. Complementary to cardiac catheterization and Doppler colour flow echocardiography. Dynamic imaging of a small bolus of IV radioactivity, usually 99mTc-DTPA, outlines the cardiac venous return, pulmonary circulation, left heart, and systemic circulation. Largely superseded by angiography and MRI.
Measurement of simple left-to-right cardiac shunts.
None.
•99mTc-DTPA administered IV as a bolus into a right antecubital vein with the shoulder abducted.
•Image immediately as a dynamic acquisition over 60s.
Normal circulation will demonstrate sequential appearance of the right heart, pulmonary outflow tract, lungs, left heart, and aorta.
Variation in the normal sequence implies cardiac shunting. Interpretation must be performed in conjunction with definitive knowledge of the patient’s anatomy, e.g. echocardiography with Doppler colour flow.
Relatively non-invasive technique for serial follow-up of congenital heart disease. Mathematical analysis of the data allows quantification of shunt size and is important for consideration and timing of corrective surgery.
One of the most widely requested nuclear medicine studies. Sensitivity and specificity reduced in coexisting lung disease, when CTPA is more useful. All patients should have had a chest radiograph within 24h to aid V/Q interpretation and exclude other causes of pleuritic chest pain and hypoxia, e.g. pneumothorax.
Lung perfusion shown by injection of 99mTc particles which are trapped by the pulmonary capillary bed. Ventilation shown using radiolabelled gases or aerosols.
•Suspected pulmonary embolism (PE).
•Preoperative lung function assessment.
None. Relative contraindication in right-to-left intra-cardiac shunts; caution in severe pulmonary hypertension.
•Lie the patient supine and inject 99mTc-macroaggregated albumin (MAA) IV.
•Obtain gamma camera perfusion images in four views.
•Ventilation images are obtained in same projections by continuous breathing of 81mKr gas or using 99mTc aerosol or 133xenon gas.
Homogeneous, matched V/Q patterns (see Fig. 14.28).
Four abnormal patterns recognized:
•Segmental perfusion loss with preserved ventilation: PE (see Fig. 14.29).
•Segmental matched perfusion and ventilation loss: pulmonary infarction/infection.
•Segmental/subsegmental ventilation loss with preserved perfusion: infection.
•Non-segmental, patchy, matched perfusion, and ventilation loss: COPD (see Fig. 14.29).
Quick, non-invasive. Normal scan virtually excludes PE.
Specificity reduced in underlying lung disease—COPD, asthma giving indeterminate results. False +ves with tumour, bullae, vasculitides, fibrotic lung disease, and old unresolved PE.
Fig. 14.29 Lung scans: (a) showing matched, non-segmental V/Q defects in COPD; and (b) showing segmental V/Q mismatch––extensive bilateral pulmonary thromboembolism and unmatched perfusion loss.
Bajc M, Neilly JB, Miniati M, et al. EANM guidelines for ventilation/perfusion scintigraphy: Part 1. Pulmonary imaging with ventilation/perfusion single photon emission tomography. Eur J Nucl Med Mol Imaging 2009; 36: 1356–70.
Largely research procedure.
Suspected pulmonary AV shunting.
None.
Inject 99mTc-MAA IV; consider manoeuvres to reduce particle number. gamma camera lung, abdomen, and head imaging. Calculate relative uptake in lungs, kidneys, and brain. Express as fraction of cardiac output to quantify shunt fraction.
Kidneys and brain not normally visible on lung perfusion imaging.
Abnormal extrapulmonary activity implies degree of shunting. Intensity of uptake rises with shunt severity (see Fig. 14.30).
Non-invasive, quantitative. Can be used to monitor response to intervention.
Injection extravasation invalidates shunt calculation.
Altered alveolar permeability affects gas exchange. Also shown by lung transfer factor measurement.
•PCP infection: rapid screening in high-risk patients with normal CXR.
•Monitor treatment response in CFA.
None.
Patient breathes 99mTc-DTPA aerosol. Gamma camera images of the thorax over 1h. Computer data analysis generates lung clearance curves, reflecting the integrity of the alveolar cell barrier.
Clearance curves used to calculate the permeability index. Individual results, compared with centre-defined normal range.
Accelerated clearance in PCP, which ↓ with successful treatment.
Non-invasive. Allows rapid PCP diagnosis.
Non-specific, e.g. accelerated clearance in smokers.
Lymphoedema can be congenital or acquired. The lymphatic system normally drains subcutaneous tissues → local lymphatic channels and regional nodes. Lymphatic channels can be imaged using radiolabelled colloid particles ( Sentinel node imaging, p. 890).
Unexplained limb swelling, e.g. lymphatic hypoplasia.
None.
99mTc-nanocolloid injection SC into a finger or toe web space on the affected and contralateral limbs. Regional gamma camera imaging at 10min intervals over 1h.
Normally rapid clearance via lymphatic channels to regional nodes (see Fig. 14.31a).
Slow clearance and failed regional node uptake in hypoplastic systems or metastatic regional node infiltration, dermal backflow (see Fig. 14.31b), depending on clinical context.
Much easier than conventional (contrast) lymphography—avoids lymphatic channel cannulation.
Lymphatic drainage may be disrupted by surgery or radiotherapy.
Fig. 14.31 (a) Normal lymphoscintograms. (b) Abnormal study: bilateral dermal backflow with non-visualization of lymphatic channels and lymph nodes.
DMSA is concentrated by the proximal convoluted tubules in the renal cortex. 99mTc-DMSA provides good definition of functioning renal parenchyma. It should be used in conjunction with anatomical imaging, e.g. ultrasonography, to differentiate between scarring, cysts, or calculi.
•UTI: ‘gold standard’ for renal scarring.
•Measurement of relative renal function.
•Renal duplication assessment.
None, but avoid dehydration.
99mTc-DMSA injected IV. Static anterior, posterior, and posterior oblique images acquired 2–4h later.
Visual image evaluation, assessing the integrity of cortical outlines for scarring (see Fig. 14.32a). Quantitative computer image analysis is used to measure relative renal function, i.e. the contribution of each kidney to overall GFR.
Cortical scars distort the renal outline (see Fig. 14.32b). Duplication may result in a non-functioning upper moiety, usually due to obstruction, or a scarred lower moiety, 2° to vesico-ureteric reflux. Relative renal function is usually 50:50 ± 5%.
Sensitive for renal scarring. Superior to US. Non-invasive.
False +ves during or immediately after acute pyelonephritis. May give cortical defects that do not progress to scarring. Splenic impression at the left upper pole may be mistaken for scarring.
Nuclear medicine offers unique ‘real-time’ imaging of renal function, i.e. visualization of uptake, drainage, and bladder emptying. Available radiopharmaceuticals include:
•99mTc-diethylenetriaminepentacetic acid (DTPA), cleared by glomerular filtration.
•99mTc-mercaptoacetyltriglycine (MAG3), cleared by glomerular filtration and tubular secretion.
•99mTc-ethylenedicysteine (EC), cleared by glomerular filtration and tubular secretion.
Tubular agents preferred, particularly in the presence of renal impairment and in the immature kidney. 99mTc-DTPA reserved for assessment of ATN, post-transplant viability, etc.
•Assessment of renal drainage: discrimination between renal dilatation and outflow obstruction.
•Measurement of relative renal function.
•RAS ( Captopril renography, p. 928).
Good hydration essential. Empty the bladder immediately before undertaking the study.
•Position the patient supine or seated erect, with the camera behind.
•Obtain good peripheral venous access. Bolus IV radiopharmaceutical injection 99mTc-MAG3 or 99mTc-DTPA, followed by 10–20mL of saline flush.
•Image immediately, acquiring real-time dynamic data for 20–30min.
•Diuretic administration is essential to distinguish dilatation from outflow obstruction.
•Post-voiding images are always required to assess the completeness of bladder emptying and may improve drainage of the upper renal tracts in high-pressure systems.
Visual inspection of renal size, perfusion, function, and drainage (see Fig. 14.33a). Quantitative computer image analysis measures relative function and transit times, and generates drainage graphs.
Uptake and excretion of activity normally rapid. Dilated systems show progressive pooling in the renal pelvis that empties following diuretic challenge. Obstructed systems show progressive tracer accumulation with no diuretic response, often associated with reduced function on the affected side (see Fig. 14.33b).
Sensitive, non-invasive, quantitative renal function assessment. Anatomical imaging, e.g. IVU, better for renal morphology, stones, etc.
Movement artefact, chronic renal failure, and dehydration reduce data reliability. Renal drainage may be gravity-dependent—always complete the study with an erect image. Drainage curves invalidated by radiopharmaceutical extravasation.
Fig. 14.33 Dynamic renogram posterior images: (a) normal, showing an early parenchymal image and later symmetrical excretion with bladder filling; (b) outflow obstruction: early image shows left hydronephrosis 2° to pelviureteric junction obstruction, with poor drainage at 60min.
RAS is a rare (<2%) cause of hypertension. Suspected in young adults presenting with hypertension, usually due to fibromuscular dysplasia. In patients >50 years, the commonest cause is atherosclerosis. Perfusion pressure is maintained by angiotensin II in RAS. Captopril is an ACE inhibitor, which blocks the conversion of angiotensin I to angiotensin II. Captopril reduces perfusion pressure, leading to a fall in the relative function and delayed tracer uptake on the affected side. Captopril administration is contraindicated in the presence of a solitary kidney.
Diagnosis of RAS (especially fibromuscular dysplasia) and prediction of response to revascularization.
Well-hydrated. Baseline BP. IV access. Stop ACE inhibitors for 48h prior to the test.
•Perform standard dynamic renogram using 99mTc-MAG3.
•Repeat renogram 1h after captopril 25mg single dose PO.
•Monitor BP—beware hypotension.
Quantitative evaluation of R:L renal function and time to peak activity in each kidney.
RAS due to fibromuscular dysplasia—fall in relative renal function and delayed time to peak renal activity of >10min.
Distinguishes generalized atherosclerosis (often poor BP outcome following angioplasty) from fibromuscular hyperplasia (good angioplasty response).
•↓ reliability in the presence of renal impairment.
The source of GI blood loss is usually identified by GI endoscopy but may be difficult to localize. Labelled red cell studies are useful when there is evidence of ongoing bleeding (typically falling Hb of 1g/L/day). The patient must be actively bleeding at the time of the study. This is a time-consuming investigation, with serial imaging beyond 24h often performed.
Localize source of active GI haemorrhage when other techniques (e.g. endoscopy or angiography) have failed.
No recent contrast barium studies. Fasting during first 2h of imaging.
Label red cells (in vitro or in vivo) using 99mTc-pertechnetate. Abdominal gamma camera blood pool imaging immediately and at intervals for up to 36h post-injection or until the bleeding source is identified.
Activity normally restricted to vascular compartment.
Any activity in the gut lumen implies active haemorrhage. Serial images helpful (see Fig. 14.34).
More sensitive and less invasive than angiography for intermittent bleeding.
•Poor red cell label: degrades image quality, could lead to false +ve.
•Limits of detection: 0.5mL/min blood loss.
The diagnosis of dysfunctional gastric emptying can be difficult. In children, delayed gastric emptying may contribute to gastro-oesophageal reflux. In adults, both gastric stasis and ‘dumping’ syndromes occur, sometimes following previous surgery. Imaging following ingestion of radiolabelled solids or liquids demonstrates the timing and pattern of gastric emptying.
Altered GI motility—delayed or accelerated gastric emptying.
Fast for 4h. Stop drugs likely to influence GI motility, e.g. domperidone, metoclopramide.
•Give radiolabelled (99mTc-DTPA) milk drink PO.
•Image the anterior abdomen immediately and at 10min intervals for 1h. Generate computer-derived clearance curves to calculate the emptying half-time.
•Delayed thoracic image helpful to exclude lung aspiration if clearance significantly delayed.
•Give 99mTc-labelled standard meal (e.g. porridge, egg) with 111In-DTPA in water.
•Anterior abdomen gamma camera imaging as before using dual isotope settings.
•Generate solid and liquid phase clearance curves.
Normal gastric emptying half-time (milk = 20min). Normal range for solids is centre-specific, depending on the standard meal composition (see Fig. 14.35a and b).
Visual image evaluation and half-time calculation.
Non-invasive and quantitative.
Vomiting during study invalidates emptying time calculations.
Fig. 14.35 (a) Normal gastric emptying study: anterior images showing clearance of 99mTc-labelled semi-solid meal into the proximal small intestine; (b) abnormal gastric emptying study: anterior images showing poor clearance of 99mTc-labelled semi-solid meal into the proximal small intestine.
The SeHCAT test is an important test for diagnosing bile acid malabsorption. SeHCAT is a taurine-conjugated bile acid analogue and it is incorporated with 75Se (gamma-emitter) into the SeHCAT molecule (radiotracer) to assess in vivo the enterohepatic circulation of bile salts. The retention of radiotracer in the body is evaluated using a conventional gamma camera.
•Ileal resection, cholecystectomy, radiation-induced bowel damage, or ulcerative colitis.
Colestyramine and colesevelam should be stopped for 3 days prior to scan.
A capsule containing radiolabelled SeHCAT (370kBq) capsule is taken PO with water, and a scan is performed to measure SeHCAT activity at 1–3h. Patients will return on day 7 to undergo a second scan to measure the percentage of SeHCAT retention.
The percentage of SeHCAT retention gives an indication as to whether the patient has bile acid malabsorption or not.
Retention values of <15% are considered abnormal and are suggestive of bile acid malabsorption (<5%, severe bile acid malabsorption; 5–10%, moderate; and 10–15%, mild). Retention values of >15% are normal.
Easy to perform and well tolerated.
Boyd GS, Merrick MV, Monks R, Thomas IL. Se-75-labeled bile acid analogs, new radiopharmaceuticals for investigating the enterohepatic circulation. J Nucl Med 1981; 22: 720–5.
Jazrawi RP, Ferraris R, Bridges C, Northfield TC. Kinetics for the synthetic bile acid 75selenohomocholic acid-taurine in humans: comparison with [14C]taurocholate. Gastroenterology 1988; 95: 164–9.
Meckel’s diverticulum is the commonest congenital anomaly of the GIT, occurring in ~2% of the population. Less than 10% contain ectopic gastric mucosa which may bleed, but diverticuli can also cause obstruction or become inflamed. Typically, childhood presentation. Nuclear medicine provides a straightforward imaging technique that targets gastric mucosal cells, which normally take up 99mTc-pertechnetate.
Unexplained abdominal pain or GI haemorrhage—after endoscopy/contrast radiology.
•H2 antagonist administration may improve specificity.
Inject 99mTc-pertechnetate IV. Immediate and serial abdominal imaging over 1h.
Normal uptake in gastric mucosa.
Focal abnormal uptake appearing at the same time as the stomach implies ectopic gastric mucosa (Meckel’s diverticulum) (see Fig.14.36), or occasionally a duplication cyst. Commonest site—right iliac fossa (RIF).
Non-invasive.
False +ves due to activity in the renal tract—lateral images usually help.
Iminodiacetic acid (IDA) compounds are cleared from the circulation by hepatocytes and secreted into the bile in the same way as bilirubin. 99mTc-labelled IDA compounds show biliary excretion through the biliary tree and gall bladder → duodenum. Useful in acute/chronic acalculous cholecystitis and to diagnose biliary atresia.
•Post-operative leak detection.
•Neonates: phenobarbital 5mg/kg/day PO for 3 days prior to study (enzyme induction).
•Adults: IV injection of 99mTc-labelled IDA complex (mebrofenin). Gamma camera imaging over 1h.
•Neonates: IV injection of 99mTc-IDA. Immediate dynamic imaging for 5min, then serial static images for up to 24h or until activity reaches the small bowel lumen.
Gall bladder and biliary tree normally shown with tracer excretion via the CBD into the duodenum by 30min post-injection. Cholecystokinin 0.5U/kg IV sometimes administered to stimulate gall bladder emptying (see Fig. 14.37a)
•Acute cholecystitis: absent gall bladder.
•Obstruction, leak, or reflux assessed visually (see Fig. 14.37b).
•Neonates: passage of activity into the gut lumen excludes biliary atresia.
•Quantification of T0 to T10 min images improves specificity for atresia diagnosis.
Non-invasive. Straightforward pattern recognition.
Delayed IDA excretion in severe jaundice: bilirubin >300µmol/L.
Fig. 14.37 (a) Normal hepatobiliary scan; (b) hepatobiliary scan showing leak post-laparoscopic cholecystectomy.
Splenectomy may be indicated in haemolytic syndromes and in refractory haemorrhagic tendencies (e.g. ITP) if associated with hypersplenic thrombocytopenia. Remnant splenic tissue, or ‘splenunculi’, can give rise to recurrent thrombocytopenia—difficult to detect on anatomical imaging. As the spleen removes abnormal red cells from the circulating blood pool, radiolabelled heat-damaged red cells can be used to localize ectopic splenic tissue.
Recurrent thrombocytopenia post-splenectomy.
None.
•Obtain a venous blood sample.
•Radiolabel red cells in vitro using 99mTc-pertechnetate.
•Image the anterior abdomen 30min later.
Damaged red cells taken up by splenic remnants (see Fig. 14.38).
Investigation of choice for splenunculus detection.
Enlarged left lobe of the liver may obscure a small splenic remnant.
Largely superseded by ultrasonography and cross-sectional imaging. Maps reticuloendothelial tissue within the liver (Kupffer cells) and spleen, to identify SOLs and confirm the presence or absence of functioning splenic tissue.
Liver SOLs—now largely replaced by US, CT, or MRI.
None.
99mTc-colloid injected IV. Abdominal gamma camera images 30min post-injection.
Normal, homogeneous liver and spleen uptake (see Fig. 14.39).
Focal ↓ uptake in SOLs. ↑ spleen and bone activity in portal hypertension. Focal ↑ uptake in the caudate lobe pathognomonic of Budd–Chiari syndrome.
Cheap.
Non-specific. Largely superseded by anatomical imaging.
Localization and assessment of acute or chronic infection/inflammation can be difficult. Nuclear medicine techniques show inflammation but do not differentiate infective from non-infective causes. Radiolabelled autologous leucocytes are injected and imaged. The normal distribution includes the liver and spleen, making peri-diaphragmatic collections difficult to identify. Delayed imaging useful in chronic low-grade infection, e.g. osteomyelitis, where cell migration to the site of inflammation is slow.
•IBD to determine disease activity, extent, severity.
None. Avoid recent barium contrast radiology.
•Obtain 40–60mL of blood sample.
•Separate the white cell layer, and radiolabel in vitro using 99mTc-exametazime (HMPAO) or 111In-oxine.
•Image 1 and 3h later (IBD), or 2, 4, and 24h for intra-abdominal sepsis/osteomyelitis.
Physiological uptake in the RES. Variable GI and renal excretion, depending on the radiopharmaceutical used (see Fig. 14.40a).
Focal ↑ uptake indicates sepsis. Diffuse ↑ gut uptake reflects the extent and activity of IBD (see Fig. 14.40b).
Very sensitive in IBD. Non-invasive, useful in sick patients, e.g. acute exacerbation of IBD.
•False −ves: leucopenia and poor white cell label, perihepatic and perisplenic collections obscured by normal liver and spleen uptake.
•False +ves: physiological gut and renal activity.
•Damaged white cells during labelling causing lung sequestration.
•99mTc-exametazime (HMPAO) preferred for routine imaging and IBD—lower radiation dose and earlier result than 111In-oxine label.
•Reserve 111In-oxine for low-grade bone sepsis localization.
•Requires aseptic facilities and trained personnel.
•Risk to staff (blood handling) and patient (contamination, re-injection into wrong patient).
Fig. 14.40 Labelled leucocyte imaging: (a) normal, and (b) acute inflammatory bowel disease—intense uptake in small and large bowel loops (Crohn’s disease).
Previously used to diagnose and monitor sarcoid and lymphoma, but increasingly superseded by 18F-FDG PET ( Labelled leucocyte imaging, pp. 944–945) and cross-sectional imaging. Sometimes useful in ‘pyrexia of unknown origin’ (PUO), e.g. immunocompromised patient where there is a suspicion of Pneumocystis jiroveci infection (cf. lung permeability studies).
•PUO and infection localization, especially in AIDS.
None.
•Inject 67Ga-citrate IV. Gamma camera imaging at 48–96h with tomography.
•Non-specific gut retention reduced by laxative administration.
Normal uptake in lacrimal glands, nasal mucosa, blood pool, liver, spleen, testes, ♀ perineum, breast (see Fig. 14.41a).
•Focal lymph node uptake in lymphoma and sarcoid distinguishes active disease from post-therapy scarring/fibrosis (see Fig. 14.41b).
•In AIDS, ↑ lung uptake indicates infection—PCP, CMV, mycobacterium—chest radiograph correlation essential.
•↑ activity in IBD and focal sepsis; largely superseded by WBC imaging.
Excellent, non-invasive marker of disease activity in lymphoma—but likely to be superseded by 18F-FDG.
Poor specificity. High radiation dose often difficult to justify when alternative techniques available. Prolonged test (48–96h).
Fig. 14.41 (a) Normal 67Ga scan; (b) abnormal tracer uptake in the lacrimal glands, parotid glands, mediastinum, and lungs, in keeping with known sarcoidosis.
Epiphora may arise from excessive tear production or inadequate drainage due to lower lid ectropion or nasolacrimal obstruction, i.e. nasal puncti, lacrimal sac, nasolacrimal ducts. Straightforward technique to assess function of the nasolacrimal apparatus.
Epiphora.
None.
One to two drops of 99mTc-labelled DTPA or pertechnetate instilled into the outer canthus of each eye. Immediate dynamic gamma camera imaging for 20min, with delayed static scans as required.
Normal rapid radiopharmaceutical clearance through the nasolacrimal apparatus.
Delayed clearance implies obstruction—level of dysfunction usually identified, i.e. punctum, lacrimal sac, nasolacrimal duct (see Fig. 14.42a and b).
Non-invasive. Avoids nasolacrimal duct cannulation (cf. dacrocystography).
Obstructed systems result in excess radiolabelled tears on the cheek, altering drainage times.
Fig. 14.42 Dacroscintigram (lacrimal drainage) showing normal lacrimal drainage on the right, and on the left obstructed drainage at the proximal nasolacrimal duct.
99mTc-pertechnetate uptake in the salivary glands reflects intact parenchyma. Salivary gland scintigraphy demonstrates both parenchymal function and excretory function. Salivary gland scintigraphy is a safe and sensitive technique to assess the function and morphology of salivary glands.
•Post-multiple radioiodine therapies.
•Irradiation of the head and neck.
None.
After IV injection of 99mTc-pertechnetate, dynamic scintigraphy is performed for 15–20min, and a sialagogue (e.g. lemon juice) stimulation is delivered and imaging is continued for further 15–20min to access excretory function. Time–activity curves for the four major salivary glands are generated.
Normal uptake of radiopharmaceutical in parotids and submandibular glands, with spontaneous excretion following lemon juice stimulation.
Delayed or reduced tracer uptake or accumulation and would be compatible with salivary gland dysfunction usually identified (see Fig. 14.43).
Easy to perform, reproducible, and well tolerated.
Fig. 14.43 The left parotid and submandibular glands show prompt tracer uptake and excretion. The right parotid gland shows poor uptake and function (arrow).
In many instances, GFR estimation from CrC is adequate, but accurate measurement is essential in renal impairment or to monitor nephrotoxic drug therapy. Glomerular compensation prevents early renal damage detection by CrC measurements—60% of filtration activity can be lost before CrC falls.
Accurate GFR to monitor renal failure, cytotoxic chemotherapy, immunosuppression, e.g. ciclosporin.
Well hydrated.
•IV injection of 51Cr-EDTA or 99mTc-DTPA.
•Venous sampling 2 and 4h later.
•Count plasma sample radioactivity and known standards in gamma counter. Correct for height and weight.
Normal GFR = 125mL/min (age-dependent).
↓ values in chronic renal failure.
More reliable and reproducible than CrC—avoids need for urine collection.
Accuracy depends on accurate measurement of dose and good injection technique—avoid any extravasation. Unreliable results in severe peripheral oedema.
Helicobacter pylori infection is associated with duodenal ulceration. Eradication therapy reduces ulcer recurrence. H. pylori produces urease which converts labelled urea → labelled CO2, detected in breath samples.
H. pylori detection—diagnosis and confirmation of eradication.
Stop antibiotics, H2 antagonists, proton pump inhibitors for 2–4 weeks.
•Patient swallows urea drink labelled with 13C (stable isotope) or 14C (radioactive isotope).
•Breath samples (CO2) collected over next 30min.
•Labelled CO2 measured by mass spectroscopy (13C) or liquid scintillation counting (14C).
Normal range varies according to local protocol.
↑ exhaled CO2 levels imply abnormal urea breakdown by urease-producing bacteria in the stomach, e.g. H. pylori.
•Very sensitive marker of active H. pylori infection (cf. serology).
•Non-invasive (cf. endoscopy) and avoids sampling errors.
•Good for non-invasive monitoring of recurrent symptoms.
Occasional false +ves in oral H. pylori infection.
Although infrequently performed, provides evidence of abnormal red cell survival and localizes sites of red cell destruction. The investigation is prolonged, with initial in vitro red cell labelling and daily activity measurements over target organs—spleen, liver, and heart—for 14 days.
•Haemolytic anaemia (to confirm ↓ RBC survival, i.e. active haemolysis).
•Localize abnormal red cell sequestration.
•Predict response to splenectomy.
None. Avoid blood transfusion during study.
•Obtain a venous blood sample, and label the patient’s red cells with 51Cr-chromate.
•Re-inject cells and measure blood activity over 14 days using gamma counter.
•Measure activity over the liver, spleen, and heart using gamma probe daily for 14 days.
•Normal red cell half-life >24 days.
•Equal fall in the heart, liver, and spleen counts with time.
Short red cell life confirms abnormal destruction. Ratio of counts in liver:spleen indicates the site of red cell destruction.
Only available technique.
Lengthy and labour-intensive. Sensitivity reduced by blood transfusion during 14 days’ measurement period. Consistent probe positioning essential for accurate organ sequestration curves.
Polycythaemia is suspected when Hb and Hct are raised. Routine laboratory screening does not differentiate true polycythaemia, i.e. elevated red cell mass, from apparent, stress, or pseudo-polycythaemia, i.e. reduced plasma volume. Radiolabelled red cells can be used to measure red cell mass. Plasma volume can be calculated from the Hct or measured independently using radiolabelled human serum albumin.
Polycythaemia, to distinguish between true polycythaemia (↑ RBC mass) from apparent polycythaemia (↓ plasma volume).
Avoid recent therapeutic venesection. Less sensitive in patients already receiving myelosuppressive therapy.
•Obtain 10 mL of venous blood.
•Radiolabel red cells using 99mTc or 51Cr.
•Re-inject radiolabelled blood and, if required, 125I-albumin.
•Obtain venous samples at 15 and 30min.
•Count activity in blood samples, compared with known standards, using gamma counter to establish plasma and red cell volumes.
Compare measured red cell mass and plasma volume with predicted values for height and weight.
Distinguish relative polycythaemia (due to ↓ plasma volume) from genuine elevation of red cell mass.
Only technique available.
Recent venesection or myelosuppressive therapy reduces test reliability. Plasma volume measurement unreliable in severe peripheral oedema.
Bile salts are synthesized and stored in the liver and are essential for adequate GI absorption. They are excreted into the gut as conjugated, water-soluble bile salts and recycled by the enterohepatic circulation with terminal ileal reabsorption. Bile salt deconjugation products are insoluble and cannot enter the enterohepatic circulation, leading to bile salt malabsorption. Bacterial overgrowth after small bowel surgery or terminal ileal disease can ↑ deconjugation.
The 14C-labelled synthetic bile acid glycocholine is administered PO. Rapid transit into the large bowel will result in breakdown of the label by the normal large bowel flora and a rise in detected exhaled 14CO2. Small bowel bacterial overgrowth, e.g. due to a ‘blind loop’, will also result in ↑ liberation of 14CO2.
•Avoid antibiotics for 1 month before study.
•Give oral 14C-labelled glycocholic acid in water.
•Count 14CO2 activity in breath samples over 6h using β liquid scintillation counter.
Glycocholate is deconjugated into 14C glycine and cholic acid by small intestine bacteria, releasing expired 14CO2. Correct result for age-related variations in endogenous 14CO2 production.
↑14CO2 levels imply bacterial colonization or bile salt malabsorption.
Accurate. Only available test.
False −ves (unusual).
