Radionuclide Imaging of Endocrine Disorders Bin.Liu, MD, PhD, Department of Nuclear Medicine West China Hospital, Sichuan University Email: bin.liu@aliyun.com 2018/6/23 1

Diagnosis and Therapy with Nuclear Medicine(NM) Diagnosis and Therapy with Unsealed Sources Clinical Problem Radiopharmaceutical Instrumentation 2

Outline of NM in endocrinology Organs: Thyroid Parathyroid Adrenal Gland Nuclear Medicine: Tracers, technical aspects Relationship to patient diagnostic pathways and other imaging modalities Contribution to management and treatment 3

Thyroid physiology Anatomy Histology 4

Thyroid physiology Iodine turnover: Uptake(trapping): NIS Organification: T4, T3 Deposition and release 5

Iodine metabolism in thyroid Increased iodine uptake: iodine deficiency, hyperthyroidism Decreased uptake: iodine saturated thyroid (drugs, food), hypothyroidism (both periferal and central) TSH fT4 fT3 Iodine uptake Hypothyroidism High Low Low Low Hyperthyroidism Low High High High 6

Thyroid imaging When should it be performed? How does it help diagnosis? What alternatives are there for imaging the thyroid? How do the results of the nuclear medicine scan affect treatment? 7

Thyroid Imaging Thyroid imaging is based on the physiologic process of thyroid hormone production The thyroid tissue cannot differentiate between non-radioactive and radioactive iodine 8

Thyroid Imaging Indications: Contraindications: goiter (palpable, US finding > 10 mm) hyperthyroidism (Graves disease, autonomous adenoma) subacute thyroiditis (deQuervain) ectopic thyroid gland, evaluation of substernal mass neonatal hypothyroidism preceding 131I therapy – iodine uptake postoperative search for functioning metastases Contraindications: pregnancy breastfeeding 9

Thyroid imaging Nowadays importance is decreasing - management of thyroid diseases is changing: anatomy: US palpable or US visualized nodule: immediately FNAB supersensitive TSH assay, fT4, fT3: uptake study is not needed anti-TPO, TRAB – differentiate Graves disease from other types of hyperthyroidism but still essential: reveal functional autonomous areas in thyroid iodine uptake prior to radioiodine therapy (number is increasing) whole body 131I scan after thyroidectomy for malignancy looking for ectopic thyroid tissue advantage: quick, cheap 10

Thyroid imaging-patient preparation Only scintigraphy: no withdrawal of anti-thyroid drugs (propylthiouracil, methimazol) Withdrawal thyroid hormones: T4 for 4 wks T3 for 2 wks Avoid iodine containing drugs, food (200 ug/day) for 4 wks (special: amiodarone-several months) Important: History (physical examination) Thyroid US finding Image of previous thyroid scintigraphy Hormone levels: TSH, fT3,fT4 11

Thyroid scintigraphy -Radiopharmaceuticals Isotope Source T1/2 Energy (keV) Use Comment 131I (NaI) Reactor 8.1 Days γ: 364 β: 606 imaging uptake therapy high dose β-emission 123I(NaI) Cyclotron 13.3 h 159 best expensive poorly available 99mTc(99mTcO4) Generator 6 h 140 daily routine cheap low dose 2018/6/23 12

Thyroid scintigraphy - dosimetry Radiophar- maceutical Administered activity (MBq) Organ receiving the largest radiation dose (mGy/MBq) 131I 1.8-7,4 p.o. 210(thyroid) 123I 7.5-25 p.o. 1.9 (thyroid) 99mTCO4 75-370 i.v. 0.06(upper large intestine) ADULTS Radiophar- maceutical Administered activity (MBq/kg) Organ receiving the largest radiation dose (mGy/MBq) 131I 0.025-0.1 p.o. 1100(thyroid) 123I 0.1-0.3 p.o. 9.8 (thyroid) 99mTCO4 1-5 i.v. 0.21(upper large intestine) CHILDREN 13

Thyroid imaging – instrumentation planar gamma camera SPECT collimator pinhole (magnification, but distortion) parallel, long holes (snout-nosed) – special for thyroid workup of acquired data: software background subtraction filtering 14

Time of acquisition after Thyroid imaging – acquisition planar: A-P view, sitting or supine position upper border: submandibular gland lower border: jugulum large field of view: in case of suspected retrosternal spread or ectopic thyroid RAO, LAO marker: sternal notch (thyroid cartilage, nodules) Radiopharmaceutical Time of acquisition after administration Minimal count number 131I 24 hours 50 000 123I 2-4 hours 50 000 - 100 000 99mTcO4 15-30 min (i.v.) 100 000 - 200 000 15

Normal thyroid scintigraphy normal size homogenous appearance sharply defined borders straight or convex lateral margins 16

Non-visualizing thyroid Low thyroid uptake Thyroiditis Suppressing medication Surgical or radioiodine ablation 17

Thyroid hot nodule 18

Thyroid cold nodule 19

Multinodular goiter 20

Autoimmune thyroid disease is a spectrum Hyperthyroidism Grave’s disease Euthyroidism Hypothyroidism Hashimoto’s disease

Diffuse goiter Graves Disease 22

Congenital Thyroid Disease 1 month-old with TSHs 52.3 µIU/ml. Thyroid imaging study reveals radiotracer uptake in the neck, in the expected location and configuration of the thyroid gland. Dyshormonogenesis. 23

Congenital Thyroid Disease 24 days old with TSHs > 60 µIU/ml and T4 < 0.25 µg/dl. A Tc-99m study reveals there is no radiotracer uptake in the neck Agenesis. 24

Iodine scintigraphy for differentiated thyroid carcinoma (DTC) 131I whole body scintigraphy after ablative radioiodine therapy – to detect the presence and location of functioning thyroid tissue (cancer), recurrences and/or metastases DTC (papillary, follicular adenocarcinoma) therapy: surgery (possible total thyroidectomy) ablative radioiodine therapy – posttherapeutic whole body scan suppressive LT4 medication follow up: neck US serum thyroglobulin level whole body 131I scintigraphy 25

Iodine scintigraphy for DTC Anterior Posterior Anterior Posterior 2018/6/23 26

Parathyroid scintigraphy Hyperparathyroidism (HPT): high PTH level primary: serum Ca2+ ↑ and PTH ↑ – usually adenoma or carcinoma secondary: serum Ca2+ ↓ and PTH ↑ – usually renal failure → parathyroid hyperplasia tertiary: after secondary HPT one or more of the hyperplastic parathyroid glands become autonomous → like primary Diagnosis: 1. laboratory (serum Ca2+, PTH) 2. localisation of hyperfunctioning gland(s) – scintigraphy Therapy: surgery, (medical: calcimimetics) Purpose of parathyroid scintigraphy: localisation of parathyroid adenoma (or multiglandular disease) radio-guided surgery 27

Parathyroid scintigraphy 99mTc-MIBI (sestamibi): uptake both in parathyroid and thyroid tissue affinity to mitochondria – accumulation in tissues with high density of cells, high energy metabolism (e.g. malignancies) Techniques: dual-phase: 99mTc-MIBI washout dual-isotope: 99mTc-MIBI - 99mTc-pertechnetate subtraction 28

Parathyroid scintigraphy Basics: 99mTc-MIBI accumulates both in thyroid and parathyroid hyperfunctioning tissue 99mTc-pertechnetate accumulates only in thyroid 99mTc-MIBI - 99mTc-pertechnetate neck scintigraphy image digital subtraction → hyperfunctioning parathyroid Other radiopharmaceuticals: instead of 99mTc-MIBI: 99mTc-tetrofosmin, 201TlCl instead of 99mTc-pertechnetate: 123I Dose: MIBI: 500-700 MBq, pertechnetate: 60-100 MBq Acquisition: sequential (both sequence is acceptable) 1. pertechnetate, 2. MIBI – patient in the same position 1. MIBI, 2. MIBI washout, 3. pertechnetate – patient gets up in between 29

Parathyroid scintigraphy 99mTc-MIBI dual-phase imaging 15 min 2 H

Parathyroid adenoma

Parathyroid adenoma

Adrenomedullar scintigraphy Radiopharmaceutical: MIBG (metaiodobenzylguanidine) structurally resembles norepinephrine active uptake by neuroendocrine cells, stored in neurosecretory granules accumulation in cells of sympathoadrenal system and other neuroendocrine cells (chromaffin, APUD, GEP, DNS) and tumours (carcinoid) labeled with 123I : diagnosis (γ-emission) 131I : diagnosis, therapy (γ + β-emission) 33

Adrenomedullar scintigraphy: Indications detection, localisation, staging, follow up pheochromocytoma neuroendocrine tumours: paraganglioma, neuroblastoma, ganglioneuroma, etc. carcinoid tumours medullary thyroid carcinoma (MTC) Merkel cell tumour of the skin tumour uptake – isotope therapy planning evaluation of tumour response to therapy sympathetic innervation of heart, lung, salivary glands 34

MIBG scintigraphy: Pheochromocytoma Anterior Posterior A 12 year-old girl who was investigated for a hypertension. Scintigraphy demonstrated a heterogeneous focus of increased tracer uptake in the right adrenal mass identified on MR. 35

MIBG scintigraphy: Neuroblastoma Anterior Posterior A 5 month-old baby who was investigated for an abdominal mass. Scintigraphy showed a left adrenal mass and an enlarged liver with tumoral infiltration. 36

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