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Nuclear medicine training in the European Union: 2015 update

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Corresponding author

Correspondence to Alain Prigent.

Additional information

A related editorial can be found at DOI 10.1007/s00259-012-2076-1.

Appendices

Annex I—diagnostic applications

Central nervous system

  • Brain perfusion

    • Radiopharmaceuticals:

      • 99mTc-Hexamethylpropyleneamineoxime (99mTc HMPAO) or 99mTc-ethyl cysteine dimer (99mTc ECD), 15O-H2O (15O water)

    • Indication:

      • Evaluation of cerebrovascular disease

      • Presurgical localization of epileptogenic foci

      • Dementia

      • Traumatic brain injury

      • Inflammation

      • Assessment of brain death

    • Possible intervention:

      • Carbonic anhydrase inhibitor (acetazolamide, Diamox®) for testing cerebrovascular flow reserve

    • Methodology:

      • SPECT or SPECT/CT

  • Dopamine transporter

    • Radiopharmaceuticals:

      • 123I-2β-carboxymethoxy-3β-(4-iodophenyl) tropane (123I-β-CIT) or 123I-N-ωfluoropropyl-2β-carbome-thoxy-3β-(4-iodophenyl) nortropane (123I-FP-CIT)

    • Indications:

      • Differentiate neurodegenerative parkinsonian syndromes from patients with parkinsonian symptoms unrelated to neurodegeneration (essential tremor, vascular parkinsonism, side effects of neuroleptica) but unable to differentiate among Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy

      • Early diagnosis of Parkinsonian syndromes

      • Differential diagnosis between dementia of Lewy bodies and other dementias

    • Methodology:

      • SPECT or SPECT/CT

  • D2 receptor imaging

    • Radiopharmaceuticals:

      • 123I-(S)-2-hydroxy-3-iodo-6-methoxy (1-ethyl-2-pyrrolidinylmethyl) benzamide) (123I-IBZM), 123I- (S)-N-((1-ethyl-2-pyrrolidinyl) methyl)-5-iodo-2,3-dimethoxybenzamide (123I epidepride)

    • Indications:

      • Differentiation of Parkinson’s disease from essential tremor or other neurodegenerative parkinsonian syndromes (e.g. multiple system atrophy, progressive supranuclear palsy)

    • Methodology:

      • SPECT or SPECT/CT

  • brain metabolism

    • Radiopharmaceutical:

      • 2-deoxy-2-18F-fluoro-D-glucose (18F-FDG), 11C methionine (18F-MET) or O-18F-fluoro-L-tyrosine (18F-FET)

    • Indications:

      • FDG:

        • Presurgical assessment (functional deficit zone) of medical refractory complex partial seizures (should be combined with ictal SPECT/CT with 99mTc-HMPAO or 99mTc-ECD)

        • Differentiate cerebral tumour from infection in immunocompromised patients with indeterminate lesions on CT and/or MR

        • CNS lymphoma

      • MET or FET

        • Identify the grade of malignancy of brain tumours

        • Suspected relapse of brain tumour

        • Assess transformation of low-grade glioma to high-grade glioma

    • Methodology:

      • PET/CT or PET/MRI

  • Cisternography and CSF leak

    • Radiopharmaceutical:

      • 111In- or 99mTc-labelled diethylenetriaminepentaacetic acid (111In- or 99mTc-DTPA)

    • Indications:

      • Hydrocephalus patients with normal pressure hydrocephalus to determine whether the patient might benefit from CSF shunting or not

      • Shunt patency

      • Cerebrospinal fluid leak

    • Methodology:

      • Planar imaging or SPECT/CT

Bone and joints

  • Bone scintigraphy

    • Radiopharmaceutical:

      • 99mTc-bisphosphonates

    • Indications:

      • Neoplastic disease

      • Post-traumatic assessment

      • Arthritides

      • Reflex sympathetic dystrophy

      • Osteomyelitis

      • Unexplained bone pain

    • Methodology:

      • Depending on the indication, flow images and blood pool images may be useful. Delayed images (skeletal phase) may include spot images, possibly with a pinhole collimator, whole-body images and SPECT or SPECT/CT, in varying combinations.

Cardiovascular system

  • Myocardial perfusion

    • Radiopharmaceuticals:

      • 201Tl or 99mTc-sestamibi or 99mTc-tetrofosmin for SPECT

      • 82Rb or 13N-ammonia for PET

    • Indications:

      • Depict the distribution of blood flow in the myocardium at rest and or during stress to assess myocardial ischaemia and scar

    • Intervention:

      • Stress testing performed either by exercise or pharmacologically using vasodilators (adenosine or dipyridamole) or inotropic (dobutamine ± atropine) drugs

    • Methodology:

      • SPECT synchronized to ECG (gated SPECT or gSPECT)

      • PET/CT with ECG gating whenever possible

  • Myocardial viability

    • Radiopharmaceuticals:

      • 201Tl or 99mTc-sestamibi or 99mTc-tetrofosmin

      • 18F-FDG

    • Indications:

      • Identify myocardium with potentially reversible contractile dysfunction in patients with chronic coronary artery disease (CAD)

    • Intervention:

      • Nitrate administration for SPECT (optional)

      • Fasting followed by glucose loading and insulin injection for PET

    • Methodology:

      • SPECT at rest, with either thallium after reinjection (optional) and/or redistribution imaging between 4 and 24 h after injection

      • PET

  • Cardiac function

    • Equilibrium radionuclide angiography

      • Radiopharmaceuticals:

        • In vivo or in vitro 99mTc-labelled red blood cells (99mTc RBC) or 99mTc-human serum albumin (99mTc-HSA)

      • Indications:

        • Measurement of left and right, diastolic and systolic, global and regional ventricular function. The most commonly measured parameter being the Left ventricular ejection fraction (LVEF)

      • Interventions:

        • Usually performed at rest. Stress study is possible either exercise on a bicycle ergometer or pharmacologically by injecting an inotropic agent.

      • Methodology:

        • ECG-gated planar imaging in LAO or gated SPECT imaging

    • First pass radionuclide angiography

      • Radiopharmaceuticals:

        • 99mTc-DTPA, 99mTc-pertechnetate, 99mTc-labelled myocardial perfusion agents

      • Indications:

        • Measurement of left and right, diastolic and systolic, global and regional ventricular function

        • Measurement of left to right shunt

      • Interventions:

        • Usually performed at rest

      • Methodology:

        • Planar dynamic acquisition with ECG gating is necessary for ventricular function

    • Myocardial perfusion SPECT, see above

    • Myocardial perfusion PET, see above

Respiratory system

  • Lung scintigraphy

    • Radiopharmaceutical:

      • 99mTc-macroaggregated albumin (99mTc-MAA) for perfusion imaging

      • 81mKr, 99mTc-labelled ultrafine carbon suspension (Technegas®) or 99mTc-DTPA aerosol for ventilation imaging

    • Indications:

      • Pulmonary embolism diagnosis

      • Quantify regional lung function prior to surgery or radiation therapy

      • Evaluate cystic fibrosis

    • Methodology:

      • Static images of ventilation and perfusion when both ventilation and perfusion agents are labelled with 99mTc. When the ventilation agent is 81mKr, alternating imaging is possible. SPECT or SPECT/CT is increasingly used.

Gastrointestinal and hepatobiliary system

  • Salivary gland scintigraphy

    • Radiopharmaceuticals:

      • 99mTc-pertechnetate

    • Indications:

      • Sjögren’s disease

      • Pleomorphic adenoma

      • Wharton’s tumour

      • Adenoid cystic carcinoma

      • Mucoepidermoid carcinoma

    • Methodology:

      • Planar dynamic imaging followed by delayed static imaging

  • Oesophageal transit scintigraphy

    • Radiopharmaceuticals:

      • 99mTc-sulphur colloid

    • Indications:

      • Achalasia

      • Diffuse oesophageal spasm

      • Scleroderma

      • Diabetes mellitus

    • Methodology:

      • Planar dynamic imaging during liquid swallowing phases

  • Gastro-oesophageal reflux scintigraphy

    • Radiopharmaceuticals:

      • 99mTc-sulphur colloid

    • Indications:

      • Gastro-oesophageal reflux evaluation

    • Methodology:

      • Planar dynamic imaging after liquid nutrition

  • Enterogastric reflux scintigraphy

    • Radiopharmaceuticals:

      • 99mTc-hydroxy-iminodiacetic acid (99mTc-HIDA) or 99mTc-iminodiacetic acid (99mTc-IDA)

    • Indication:

      • Assessment of enterogastric reflux

    • Methodology:

      • Planar dynamic imaging.

  • Gastric emptying scintigraphy

    • Radiopharmaceuticals:

      • 99mTc-sulphur colloid

    • Indications:

      • Dumping syndromes

      • Gastroparesis (diabetic, postsurgical or idiopathic)

      • Functional dyspepsia

      • Pyloric stenosis

    • Methodology:

      • Planar dynamic imaging after liquid/solid phase nutrition

  • GI bleeding scintigraphy

    • Radiopharmaceuticals:

      • 99mTc-sulphur colloid or 99mTc-labelled RBC

    • Indications:

      • Lower or upper GI tract bleeding assessment

    • Methodology:

      • Planar dynamic imaging and preferably SPECT/CT

  • Meckel’s diverticulum scintigraphy

    • Radiopharmaceuticals:

      • 99mTc-pertechnetate

    • Indications:

      • Assessment of ectopic gastric mucosa (Meckel’s diverticulum)

    • Interventions:

      • Premedication with oral cimetidine (20 mg/kg) 48 h before or ranitidine (1 mg/kg) 1 h before test

    • Methodology:

      • Sequential dynamic imaging and preferably SPECT/CT

  • Spleen imaging

    • Radiopharmaceuticals:

      • 99mTc-sulphur colloid or 99mTc-labelled RBC

    • Indications:

      • Confirming the patency of hepatic arterial perfusion catheters and evaluating the pattern of blood flow via these catheters, including aberrant perfusion and shunting

      • Assessing the size, shape and position of the spleen

      • Detecting, measuring and monitoring masses of the spleen

      • Identifying functioning splenic tissue (accessory spleen)

      • Evaluating suspected functional asplenia

    • Methodology:

      • Planar static images or SPECT/CT

  • Hepatobiliary system

    • Radiopharmaceuticals:

      • 99mTc-HIDA or 99mTc-IDA, 99mTc-mebrofenin, 99mTc-lidofenin/99mTc-disofenin, 99mTc-MAA (HSA)

    • Indications:

      • Evaluating hepatic biliary system function and patency

      • Calculation of gall bladder ejection fraction (GBEF)

      • Assessment of biliary enteric bypass (Kasai procedure)

      • Bile leakage

      • Biliary atresia

      • Sphincter of Oddi dysfunction

      • Enterogastric (duodenogastric) reflux assessment

      • Chronic cholecystitis

      • Hepatic perfusion in planning selective internal radiation or drug therapy in liver tumours (HSA)

    • Interventions:

      • Cholecystokinin or morphine or phenobarbital when appropriate

    • Methodology:

      • Planar dynamic imaging

Nephro-urinary and genital system

  • Assessment of renal function and transit

    • Radiopharmaceuticals:

      • 99mTc-DTPA, 99mTc-betiatide, 99mTc-bisicate, 123I-iodo-ortho-hippurate

    • Indications:

      • Estimation of differential renal function

      • Assessment of renal and pyelocalyceal transits

      • Anterograde (descending or direct) radionuclide cystogram

    • Pharmaceutical interventions:

      • Angiotensin-converting enzyme inhibitor (captopril scintigraphy) po administration

      • Furosemide (furosemide scintigraphy) IV injection

    • Methodology:

      • Planar dynamic imaging

  • Renal cortical imaging

    • Radiopharmaceuticals:

      • 99mTc-dimercaptosuccinic acid (99mTcDMSA)

    • Indications:

      • Estimation of sequelae of pyelonephritis and/or vesicoureteral reflux

      • Detection of parenchymal lesions in untypical acute pyelonephritis

      • Detection of ectopic kidneys

      • Estimation of differential renal function (secondary choice)

    • Methodology:

      • Planar imaging and SPECT optional

  • Retrograde (ascending or direct) radionuclide cystogram

    • Radiopharmaceuticals:

      • 99mTc-sulphur colloid, 99mTc-DTPA or 99mTc-pertechnetate

    • Indications:

      • Detection (during feeling and voiding) and quantification of vesicoureteral reflux

    • Methodology:

      • Planar dynamic imaging

  • Clearance methods (plasma and urinary methods)

    • Radiopharmaceuticals:

      • 51Cr-ethylenediamine tetraacetic acid (51Cr-EDTA), 99mTc-DTPA, 123I-iodo-ortho-hippurate

    • Indications:

      • Measurement of glomerular filtration rate (GFR) with 51Cr-EDTA (or 99mTc-DTPA as second choice)

      • Estimation of the plasma renal flow rate (ERPF) with 125I-iodo-ortho-hippurate

    • Methodology:

      • Blood samples (and time urinary collections, optional), in vitro counting and kinetics modelling

      • Planar dynamic imaging (camera-based techniques with radiopharmaceuticals labelled with either 99mTc or 125I)

Endocrine system

  • thyroid imaging and function

    • Radiopharmaceuticals 1: 99mTc pertechnetate

      • Indications:

        • Evaluation of thyroid nodules [mainly in low thyroid-stimulating hormone (TSH) state]nd goiter

        • Locating ectopic thyroid tissue

        • Determining the function of thyroglossal cyst

      • Methodology:

        • Planar imaging scintigraphy and SPECT or SPECT/CT

    • Radiopharmaceuticals 2: 123I-iodine

      • Indications:

        • Evaluation of thyroid function

        • Locating ectopic thyroid tissue

        • Thyroid aplasia

      • Interventions:

        • Perchlorate washout

      • Methodology:

        • Planar imaging or SPECT or SPECT/CT

      Radiopharmaceuticals 3: 131I-iodine

      • Indications:

        • Dosimetry for ablative therapies

      • Interventions:

        • TSH stimulation

      • Methodology:

        • Planar imaging thyroid and/or whole-body scan, additional SPECT/CT when indicated

    • Radiopharmaceuticals 4: 99mTc-sestamibi

      • Indications:

        • Assessment of malignancy risk in thyroid cold nodules

      • Methodology:

        • Planar imaging or SPECT or SPECT/CT

  • Medullary thyroid cancer

    • Radiopharmaceuticals:

      • 123I- or 131I-metaiodobenzylguanidine (123I-MIBG), 99m Tc (V)DMSA, 111In-octreotide

      • 18F-FDG, 18F-DOPA, 68Ga-labelled somatostatin analogues

    • Indications:

      • Medullary thyroid cancer recurrence

    • Patient preparation:

      • Lugol’s solution preparation for iodine-labelled RP

    • Methodology:

      • Planar thyroid and whole-body imaging, and SPECT or SPECT/CT

      • PET or PET/CT

  • parathyroid location in hyperparathyroidism

    • Radiopharmaceuticals:

      • 201Tl, 99mTc-sestamibi

    • Indications:

      • Parathyroid adenoma or hyperplasia

      • Ectopic parathyroid gland

    • Methodology:

      • Planar imaging of neck and mediastinum (with either coregistration or subtraction when using either 99mTc-pertechnetate or 123I for double radionuclide technique), SPECT or SPECT/CT recommended

  • adrenal medulla tumour location

    • Radiopharmaceuticals:

      • 123I- or 131I-MIBG

    • Indications:

      • Phaeochromocytoma

      • Paraganglioma

      • Neuroblastoma

    • Patient preparation:

      • Protection of thyroid iodine uptake with Lugol’s solution

    • Methodology:

      • Planar imaging, whole-body imaging, SPECT or SPECT/CT

  • adrenal cortex imaging

    • Radiopharmaceuticals:

      • 131I-Noriodocholesterol

    • Indications:

      • Cushing’s syndrome

      • Primary aldosteronism

      • Hyperandrogenism

    • Patient preparation:

      • Dexamethasone suppression

    • Methodology:

      • Planar imaging, SPECT or SPECT/CT

Haematopoietic and lymphatic system

  • Body fluid volume determination

    • Radiopharmaceutical 1:

      • 51Cr-labelled RBC

    • Indications:

      • RBC volume measurement and RBC life span

    • Radiopharmaceutical 2:

      • 99mTc- or 125I-labelled HSA

    • Indications:

      • Plasma volume measurement

    • Radiopharmaceutical 3:

      • 51Cr-EDTA

    • Indications:

      • Extracellular volume measurement

    • Methodology (common to the three radiopharmaceuticals):

      • Blood sampling, in vitro counting and kinetics modelling

  • Platelet survival study

    • Radiopharmaceutical:

      • 111In-labelled platelets

    • Methodology:

      • Planar imaging

  • Splenic function

    • Radiopharmaceuticals:

      • 99mTc-labelled heat-treated RBC

    • Methodology:

      • Planar imaging

  • Lymphoscintigraphy

    • Radiopharmaceuticals:

      • 99mTc-nanocolloids

    • Indications:

      • Lymphoedema

    • Methodology:

      • Planar imaging

Oncology

  • Tumour imaging and characterization

    • Radiopharmaceutical 1:

      • 18F-FDG

    • Indications:

      • Differentiating benign and malignant tumours

      • Tumour staging

      • Monitoring the effect of therapy

      • Detecting residual tumour or recurrence

    • Methodology:

      • PET/CT

    • Radiopharmaceutical 2:

      • 18F-choline or 11C-choline

    • Indication:

      • Restaging of patients with biochemical failure after local treatment of a prostate carcinoma

    • Methodology:

      • PET/CT

    • Radiopharmaceutical 3::

      • Analogues of somatostatin such as 111In-octreotide or 68Ga-somatostatin analogues

    • Indications:

      • To identify primary neuroendocrine tumours and metastases that express somatostatin subtype 2 receptors

    • Intervention:

      • To withdraw (or temporarily lower as much as possible) somatostatin analogue treatment before the scintigraphy

    • Methodology:

      • Planar imaging or SPECT/CT when using 111In-labelled somatostatin analogues

      • Whole-body PET or PET/CT when using 68Ga-labelled somatostatin analogues

    • Radiopharmaceutical 4::

      • 18F-DOPA

    • Indications:

      • To identify neuroendocrine tumours and their metastases expressing the L-type amino acid transporter 1 (LAT1)

    • Interventions:

      • Carbidopa has been reported to increase tumour uptake

    • Methodology:

      • PET/CT

    • Radiopharmaceutical 5:

      • 18F-NaF

    • Indications:

      • Detection and localization of bone metastases in cases of cancer in adults

    • Methodology:

      • PET/CT

  • Lymphoscintigraphy and intraoperative probe for sentinel lymph node localization

    • Radiopharmaceuticals:

      • 99mTc-labelled colloid particles or nanocolloid

    • Indication:

      • Surgical localization of the sentinel node

    • Methodology:

      • Planar imaging or SPECT (optional), and radioguided surgery

Inflammatory and infectious diseases

  • Infection/inflammatory site imaging

    • Radiopharmaceutical 1:

      • 18F-FDG

    • Indications:

      • Localization of abnormal foci guiding the aetiological diagnosis in cases of fever of unknown origin

      • Fever in an AIDS patient

      • Detection of the extension of inflammation in cases of:

        • Inflammatory bowel diseases

        • Vasculitis involving the great vessels

        • Vascular prosthesis

        • Sarcoidosis

      • Suspected chronic infection of bone and/or adjacent structures:

        • Osteomyelitis and/or soft tissue infection

        • Spondylitis

        • Discitis

        • Osteitis including when metallic implants are present

        • Diabetic foot with suspicion of Charcot’s neuroarthropathy

        • Painful hip prosthesis

      • Therapy follow-up of unresectable alveolar echinococcosis

    • Methodology:

      • PET or PET/CT

    • Radiopharmaceuticals 2:

      • 99mTc- (or 111In)-labelled white blood cells or 99mTc-labelled anti-granulocyte antibodies

    • Indications:

      • Localization of abnormal foci guiding the aetiological diagnosis in cases of fever of unknown origin

      • Detection of musculoskeletal infection such as septic arthritis and osteomyelitis and/or soft tissue infection

      • Diabetic foot with suspicion of Charcot’s neuroarthropathy

    • Methodology:

      • Planar whole-body imaging or SPECT or SPECT/CT

Annex II—therapeutic applications in nuclear medicine (marketed or in development)

  1. 1.

    Palliation of painful sclerotic and mixed bone metastases

    1. (a)

      89Sr-chloride

    2. (b)

      153Sm-ethylenediamine tetramethylene phosphonic acid (153Sm-EDTMP or 153Sm-lexidronam)

    3. (c)

      186Re–hydroxyethylidene diphosphonate (186Re-HEDP or 186Re-etidronate)

    4. (d)

      177mSn-DTPA

  2. 2.

    Treatment of sclerotic metastases

    1. (a)

      223Ra–dichloride

  3. 3.

    Radiosynoviorthesis

    1. (a)

      Small joints

      1. i.

        169Er-citrate and 169Er-colloids

      2. ii.

        166Ho-ferric hydroxide macroaggregate

    2. (b)

      Medium-sized joints

      1. i.

        186Re-colloids

    3. (c)

      Knee joint

      1. i.

        90Y-citrate and 90Y-silicate and 90Y-colloids

      2. ii.

        153Sm-particulate hydroxyapatite

  4. 4.

    Thyroid diseases

    1. (a)

      Well-differentiated thyroid cancer:

      1. i.

        131I

    2. (b)

      Radioiodine-refractory differentiated thyroid cancer

      1. i.

        177Lu-[DOTA0, Tyr3]octreotate or 177Lu-DOTATATE and 177Lu-[DOTA0-1-Nal3]octreotide or 177Lu-DOTANOC

    3. (c)

      Benign thyroid diseases (hyperthyroidism and volume reduction in goiter)

      1. i.

        131I

  5. 5.

    Malignant neural crest tumours (neuroblastoma, phaeochromocytoma, paraganglioma, medullary thyroid carcinoma…)

    1. (a)

      131I (131I-MIBG)

  6. 6.

    Neuroendocrine tumours [peptide receptor radionuclide therapy(PPRT) or PRRT using radiolabelled somatostatin analogues]

    1. i.

      111In-DTPA-octreotide

    2. ii.

      177Lu-[DOTA0, Tyr3]octreotate or 177Lu-DOTATATE and 177Lu-[DOTA0-1-Nal3]octreotide or 177Lu-DOTANOC

    3. iii.

      90Y-[DOTA0, Tyr3]octreotide or 90Y-DOTATOC

  7. 7.

    Hepatocarcinoma and liver metastases [selective internal radiation therapy (SIRT)]

    1. (a)

      131I-Lipiodol

    2. (b)

      90Y-microspheres

    3. (c)

      188Re-hyaluronic acid

  8. 8.

    Polycythaemia vera

    1. (a)

      32P

  9. 9.

    Melanoma

    1. (a)

      64CuCl2

  10. 10.

    Internal vectorized radiotherapy using labelled tumour-specific monoclonal antibodies

    1. (a)

      Non-Hodgkin’s lymphoma

      1. i.

        90Y-Ibritumomab tiuxetan or 90Y-epratuzumab tetraxetan

      2. ii.

        177Lu-DOTA-rituximab

      3. iii.

        211At-labelled anti-CD45 antibody

    2. (b)

      Prostate carcinoma

      1. i.

        90Y- or 177Lu-radiolabelled monoclonal antibody targeting the epitope prostate-specific membrane antigen (PSMA) (90Y or 177Lu-J591 mAb)

      2. ii.

        89Zr-desferrioxamine B-J591 mAb

    3. (c)

      Glioma

      1. i.

        211At-labelled Me1-14F(ab′)2

    4. (d)

      Head and neck carcinoma

      1. i.

        211At-labelled U36 chimeric monoclonal antibody

  11. 11.

    Disseminated cancer

    1. (a)

      211At-EGFRvIII monoclonal antibody

  12. 12.

    Prevention of reactive hyperplasia after stent placement (intravascular, intraurethral…)

    1. (a)

      188Re-filled balloon dilation

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Prigent, A., Hustinx, R., Costa, D.C. et al. Nuclear medicine training in the European Union: 2015 update. Eur J Nucl Med Mol Imaging 43, 583–596 (2016). https://doi.org/10.1007/s00259-015-3244-x

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