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Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
Microsoft PowerPoint - 09-30 Gross
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Microsoft PowerPoint - 09-30 Gross

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  • 1. 1 The Role of Nuclear Medicine in Endocrinology: Past, Present, Future Milton D. Gross, M.D. Department of Radiology and Internal Medicine, University of Michigan Department of Veterans Affairs Health System Ann Arbor, Michigan The Role of Nuclear Medicine in Endocrinology: Past, Present, Future Milton D. Gross, M.D. Conflict of Interest Disclosure Nuclear Medicine in Endocrinology The history of the development Nuclear Medicine and Endocrinology are intertwined. Much of what we do can be “traced” back to the earliest uses of radioiodine. Radionuclide techniques developed to study the function and anatomy of endocrine organs/tissues have been the basis for the diagnostic and therapeutic approach to other organ systems. Nuclear Medicine in Endocrinology What has changed over the last 6 decades are an increasing number of available radionuclides and radiolabeled compounds for imaging endocrine organ/tissue function. Increasingly more sophisticated (and expensive) imaging devices that provide impressive sensitivity, better spatial resolution, and incorporation of fused anatomy/function. Modalities for Endocrine Imaging +++++Approved PET tracers are few (FDG) Expensive, limited availability (+ CT ↑rad exposure) FDG, et al labeled agents selective uptake Detection of positron emitting tracers Positron Emission Tomography + CT +++Complementary to CT/MR Moderate resolution, delay to imaging from hrs to days (+ CT ↑rad exposure) Non-invasive depiction of in physiology Selective localization of radiopharmaceutical Single photon imaging (SPECT) + CT +++++Limited advantages over CT Resolution < CTHigh spatial resolution, no radiation, tissue characterization Radio-frequency signal by protons in magnetic field Magnetic Resonance ++++Widely employedradiation exposure, iv contrast Highest spatial resolution X-ray attenuation, anatomy based Computed Tomography ++++Valuable when non- invasive studies are equivocal Invasive, technically demanding, hemorrhage, infection Direct characterization of secretory state + stimulation Direct measurement of venous hormone levels Venous hormone sampling +++Generally obsolete for endocrine gland localization Invasive, technically demanding, Detailed depiction of vascular anatomy X-ray attenuation with iodinated contrast Angiography ++Limited utilityLimited resolution, interference by fat and bowel gas Widely available, no radiation exposure Reflection of ultrasound depicts anatomy Ultrasound Relative CostCommentsDisadvantagesAdvantagesUnderlying PrincipalTechnique PET in Endocrinology • PET is an extension of the “molecular” approach to endocrine diagnosis. • Follow in vivo receptor-ligand interaction, biodistribution and metabolism. • A confirmed biochemical diagnosis is a critical first step regardless of the modality used for localization.
  • 2. 2 PET in Endocrinology • PET provides the opportunity to create novel radiopharmaceuticals that take advantage of unique physiology/pathophysiology of endocrine organs/systems • Radioactive isotopes (11C, 13N, 15O) can be incorporated into hormones, secretogogues, receptor ligands, products of intermediatary metabolism, etc. without changing their native chemistry or metabolism. • Other positron-emitting isotopes (18F, 124I, 68Ga) can be used to label ligands in the same manner as that employed for other non-PET applications. Nuclear Medicine in Endocrinology Imaging Techniques in Thyroid Disease Radioiodine (123I+, 131I, 124I°) 99mTechnetium (Tc)+ 201Thallium (Tl) 99mTc-Sestamibi+ Probe-guided 99mTc-Tetrafosmin+ 111In-pentetreotide (PAP CA, MCT) 111In-anti-CEA monoclonal antibody (MCT) 99mTc-(V)-DMSA (MCT) 18F-fluorodeoxyglucose° Ultrasound CT (fusion/hybrid SPECT or PET) MRI +single photon emission tomography °positron emitting radiopharmaceutical Thyroid Imaging Thyroid nodules are common – 4 to 7% of adults have palpable nodules. Thyroid imaging can distinguish benign from malignant nodules on the basis of radioiodine or 99mTechnetium pertechnetate uptake, but Thyroid US and needle biopsy have supplanted radionuclide imaging for characterization of nodules and follow up in thyroid cancer Normal thyroid shows faint 18F-FDG uptake McDougall et al. Nucl Med Commun 2001;22:485-492 18F-FDG has been used to distinguish benign from malignant thyroid nodules (?) Adler L, Bloom A. Thyroid 1993;3:195-200 Bloom et al. Surgery 1993;114: 728-735 Saski et al. Nucl Med Commun 1997;18:957-963 FDG scan with (R)FDG scan with (R) hilarhilar metastasis & mild, diffuse thyroid uptakemetastasis & mild, diffuse thyroid uptake Thyroid Imaging 18F-FDG in diffuse thyroid disease Diffuse uptake in chronic lymphocytic thyroiditis? Yasuda et al. Radiology 1998;207:775-778 18F-FDG uptake depicts with autonomous thyroid tissue? Broener et al. Thyroid 1998;8:765-772 Boerner et al. Exp Clin Endoocrinol Diabetes 2000;108:191-196 Incidental thyroid 18F-FDG uptake in ~2% (102/4250) and ~1/2 with thyroid Ca Cohen et al. Surgery 2001;130:941-946 Van Den Bruel et al. J Clin Endocrinol Metab 2002;87:1517-1520 Kang et al. J Clin Endocrinol Metab 2003;88:4100-4104 Incidental diffuse prominent FDG thyroid uptake in a 77 y/o femaIncidental diffuse prominent FDG thyroid uptake in a 77 y/o female,le, HxHx colon cancer s/p surgery & adjuvantcolon cancer s/p surgery & adjuvant chemoTxchemoTx, evaluation of, evaluation of rising CEA.rising CEA. thyroid thyroid thyroid
  • 3. 3 FDG scan in a 52 y/o female with lowFDG scan in a 52 y/o female with low--grade marginal zone B cell lymphomagrade marginal zone B cell lymphoma of MALT type in (R) thyroid in the setting of Hashimotoof MALT type in (R) thyroid in the setting of Hashimoto’’ss thyroiditisthyroiditis, s/p (R), s/p (R) thyroidthyroid lobectomylobectomy.. (L) thyroid (L) thyroid (L) thyroid Thyroid Imaging 18F-FDG in well-differentiated thyroid cancer Optimally done with TSH stimulation van Tol et al. Thyroid 2002;12:381-387 Post-thyroidectomy elevated Tg; non-localizing 131I scans 18F-FDG identified metastases not seen by 131I changed management 29/37 patients Helal et al. J Nucl Med 2001;42:1464-1469 18F-FDG detected thyroid ca mets in 95% and changed therapy in 9/24 pts Frilling et al. Ann Surg 2001;234:804-811 18F-FDG uptake may predict resistance to 131I Tx/Prognosis Larson et al. Sem in Roent 2002;37:169-174 Robbins, et al. J Clin Endocrinol Metab 2006;91:498-505 MetastaticMetastatic papillary thyroid ca: 69 y/o male with previously treated papipapillary thyroid ca: 69 y/o male with previously treated papillaryllary thyroid ca, known cervical LN recurrence,thyroid ca, known cervical LN recurrence, 131131Iodine scan negative,Iodine scan negative, ↑↑ TgTg 32287700 6/006/00 10/0110/01 131131I scanI scan 10/0110/01 8181 y/oy/o manman * Papillary thyroid ca s/p resection 1992 followed by* Papillary thyroid ca s/p resection 1992 followed by 131131II TxTx * Extensive liver* Extensive liver metsmets since 1997since 1997 Robbins, R. J. et al. J Clin Endocrinol Metab 2006;91:498-505 Kaplan-Meier survival plots of thyroid cancer patients based on combined consideration of stage and FDG-PET scan result
  • 4. 4 Kaplan-Meier plot of survival of thyroid cancer patients with or without metastases Robbins, R. J. et al. J Clin Endocrinol Metab 2006;91:498-505 Thyroid Imaging 18F-FDG in well-differentiated thyroid cancer 18F-FDG in Hürthle cell cancer Identified all known lesions and local/distant metastases in 7/14 that changed management Lowe et al J Nucl Med 2003;44:1402-1406 Detection of recurrent Hürthle cell cancer by 18F-FDG by meta- analysis (multicenter study) sensitivity 92%, specificity 80%, accuracy 89%, PPV 92%, NPV 80% Plotkin et al. Thyroid 2002;12:155-161 RecurrentRecurrent metastaticmetastatic HurthleHurthle cell ca: 57 y/o male withcell ca: 57 y/o male with HxHx treatedtreated HurthleHurthle cell ca x 3 yrs.cell ca x 3 yrs. ↑↑TG, suspected R ant rib metastasis confirmed onTG, suspected R ant rib metastasis confirmed on 111111InIn-- Octreoscan and FDGOctreoscan and FDG--PET (curved arrow) which wasPET (curved arrow) which was resectedresected. FDG. FDG--PETPET detected an additional abnormal focus in the thyroid bed not seedetected an additional abnormal focus in the thyroid bed not seen on then on the 111111InIn-- OctreoscanOctreoscan or CT. Neck exploration confirmed tumor at this site.or CT. Neck exploration confirmed tumor at this site. Coincidental finding of focal intense uptake in a thyroid nodule (red arrow) in a patient with stage III NSCLC. FNAB = Hurthle cell carcinoma. Thyroid Imaging 18F-FDG in medullary thyroid cancer 18F-FDG outperformed MR/CT/MIBG for identification of lesions in pts with MTC with elevated iCT/CEA levels post-op Szakall et al. J Nucl Med 2002;43:66-71 18F-FDG > 111In-octreotide > 99mTc-DMSA > 99mTc-sestamibi for MTC Diehl et al Eur J Nucl Med 2001;28:1671-1676 18F-DOPA > 18F-FDG in 11 pts with MTC and ↑iCT levels Hoegerle et al. Eur J Nucl Med 2001;28:64-71 56 y/o man previously treated for56 y/o man previously treated for medullarymedullary thyroid cancer nowthyroid cancer now withwith ↑↑ calcitonincalcitonin..
  • 5. 5 Multimodality Imaging and Fusion Techniques • Integrated PET/CT has: - Improved lesion detection on both CT and FDG PET -Improved localization of foci of FDG uptake -Improved differentiation of physiologic vs. pathologic uptake - Improved therapeutic guidance and evaluation of therapy
  • 6. 6 Multimodality Imaging and Fusion Techniques • What about SPECT/CT? - Improved lesion detection -Improved localization of foci of radioiodine uptake -Improved differentiation of physiologic vs. pathologic uptake - Improved therapeutic guidance and evaluation of therapy Additional value of SPECT/CT in defining 131I uptake in the neck 61Total 3Equivocal 1aSkin contamination 1aPhysiological activity 10aLN involvement 2aThyroid bed Equivocal 10LN involvement 1aBone metastasis 2aThyroid bed LN involvement 29Thyroid bed 2aLN involvement Thyroid bed Neck No. patientsSPECT/CT characterizationPlanar findings Region of body aIncremental diagnostic value in 19 patients Tharp K, et. al. Eur J Nucl Med Mol Imaging Additional value of SPECT/CT in defining 131I uptake outside the neck 36Total 1aSkin contamination 2aBone metastasesEquivocal (soft tissue/bone metastases) Extremities 1aPhysiological colon activity 3aBone metastasesEquivocal (soft tissue/bone metastases) Abdomen/p elvis 10Lung metastases 2aSkin contamination 1aPhysiological breast uptake 4aBone metastases 5aMediastinal LN involvement Lung metastasesChest 2aBone metastases (maxilla and mandible) Physiological activity in buccal mucosa 5aPhysiological activity in parotid Equivocal Head/skull No. patients SPECT/CT characterizationPlanar findings Region Tharp K, et. al. Eur J Nucl Med Mol Imaging
  • 7. 7 Nuclear Medicine in Endocrinology Imaging Techniques in Hyperparathyroidism 123Iodine (I)-201Thallium (Tl) 201Tl-99mTechnetium (Tc) 99mTc-201Tl 99mTc-Sestamibi Single phase Dual phase/Dual tracer∗ SPECT+ Probe-guided 99mTc-Tetrafosmin 18F-fluorodeoxyglucose° 11C-methionine° Ultrasound CT (Fusion/Hybrid SPECT or PET) MRI ∗dual tracer imaging technique with subtraction of 123I or 99mTc activity +single photon emission tomography °positron emitting radiopharmaceutical Parathyroid Imaging 99mTc-sestamibi has made a significant impact in the management of hyperparathyroidism Used for pre-op localization/facilitated probe guided surgery and in post-op/recurrent hyperthyroidism with high efficacy 11C-Methionine shown to localize parathyroid glands in pre-op/recurrent disease Hellman et al. Surgery 1994;116:974-981 Sundin et al. J Nucl Med 1996;37:1766-1770 Cook et al. Eur J Nucl Med 1998;139:195-197 18F-FDG has been used to depict 17/18 proven parathyroid adenomas in 16 pts (94% sensitivity) and 2/4 hyperplastic glands (50% specificity) Neumann et al. Radiology 1994;192:509-512
  • 8. 8
  • 9. 9 Adrenocortical Imaging High resolution anatomic imaging has supplanted functional imaging for the evaluation of adrenocortical disease In addition to physical characteristics of adrenal masses on CT and MR semiquantitative methods (CT contrast washout) can be used to distinguish benign from malignant adrenal masses Radionuclide imaging is complementary to CT/MR and can provide additional function information Present radiopharmaceuticals for adrenocortical imaging show high sensitivity/specificity/accuracy for identifying adenomas Radiopharmaceuticals for Adrenocortical Imaging Radiopharmacuetical Metabolic activity Uptake Mechanism 131I-19-iodocholesterol LDL-receptor LDL receptor mediated 131I-6-iodocholesterol ⇓ ⇓ 131I-6β-iodomethylcholesterol (NP-59) ⇓ ⇓ 75Se-selenomethylnorcholesterol (SMC) ⇓ ⇓ 131I, 123I, 111In, 99mTc-LDL ⇓ ⇓ 11C-acetate TCA intermediate Metabolic intermediate 11C-etiomidate 11β-hydroxylase inhibitor Adrenocortical enzyme inhibitor 11C-metiomidate ⇓ ⇓ 131I-metyrapone ⇓ ⇓ 18F-fluorodeoxyglucose Glucose analog Metabolic intermediate 11C-Choline Metabolic intermediate Cellular membranes A B Incidentally discovered adrenal mass. Left adrenal adenoma: CT scan performed for staging of a head and neck tumor, revealed a 1.7 x 0.7 cm left adrenal nodule and thickening of the right adrenal gland (B, arrows). There is low grade FDG uptake in both adrenal glands (A, arrows) compatible with a benign non-FDG-avid processs. Repeat CT showed no change after 6 months of observation. Benign bilateral adrenal hypertrophy in a 53 y/o manBenign bilateral adrenal hypertrophy in a 53 y/o man withwith squamoussquamous cell cancer of base of tongue for recell cancer of base of tongue for re-- staging, recent CT: enlarged adrenalsstaging, recent CT: enlarged adrenals RR Left adrenal adenoma. Outside CT performed to evaluate lung mass revealed a 2.3 cm left adrenal mass (-9 HU - non-contrast enhanced CT. PET study shows low grade FDG uptake compatible with a non-FDG avid process. A B
  • 10. 10 Adrenocortical Imaging 18F-FDG in non-hyperfunctioning (non-hypersecretory) adrenal masses compared to NP-59 and 131I-MIBG in 54 patients NP-59 MIBG FDG #studies 24 23 26 Sens (%) 100 100 100 Spec (%) 71 94 100 Acc (%) 92 96 100 PPV (%) 89 83 100 NPV (%) 100 100 100 Maurea et al. J Nucl Med 2001;42:884-892 Results with 18F-FDG have been confirmed by others Yun et al. J Nucl Med 2001;42:175-1799 Metzer, et al. J Nucl Med 2006;47:32-37 Blake, et al. Radiology 2006;238:970-977 Adrenocortical Imaging 18F-FDG is an accurate method to evaluate adrenal masses in NSCLC 25 masses/27 pts, 23/25 (92%) metastases SUV = 6 (3 to 14) 2 false + masses (proven by biopsy) FDG – in 8 (CT < 10HU) SUV = 1.8 (0.9 to 3.7) Sensitivity for detecting metastatic disease = 100% Specificity = 80% Erasmus et al. Am J Roent 1996;168:1357-1360
  • 11. 11 Adrenocortical Imaging Etiomidate is an anesthesia-induction agent and a potent 11ß-hydroxylase inhibitor. 11C-Etomidate/metomidate demonstrate avid accumulation in adrenocortical tissues and adrenocortical tumors Zettiinig et al. Eur J Ncul Med Mol Imag 2004;31:1224-30 Minn et al. J Nucl Med 2004;45:972-979. High SUV in adenomas (>15) and in adrenal carcinoma (>20) with normal adrenal (7 to 22) Bergstrom et al. J Nucl Med 2000;41:275-282 Trampal et al. Radiology 2004;230:423-428 Jonson S, et al Nucl Med Biol 1999;26:131-138 Clinical Utility of PET in the Evaluation of Adrenal Tumors Clinical Indication Radiopharmaceutical Adrenal Cortex Distinguishing unilateral from bilateral adrenocortical disease - bilateral adrenal hyperplasia in hypercortisolism 18F-FDG - identifying unilateral adrenal adenoma in hypercortisolism 11C-metomidate and primary aldosteronism Depicting adrenal cortical function - identifying function in benign vs. malignant or 18F-FDG metastatic, incidentally discovered adrenal masses 11C-metomidate -localizing metastatic adrenocortical carcinoma 18F-FDG 11C-metomidate Radiopharmaceuticals for Sympathomedulla Imaging Radiopharmacuetical Metabolic activity Uptake Mechanism 131I-metaiodobenzylguanidine (131I-MIBG) Neuronal blocker Active transport into 123I-metaiodobenzylguanidine (123I-MIBG) ⇓ neurosecretory granules 125I-metaiodobenzylguanidine (125I-MIBG) ⇓ ⇓ 131I-aminoiodobenzylguanidine (131I-AIBG) ⇓ ⇓ 76Br-aminoiodobenzylguanidine (76Br-AIBG) ⇓ ⇓ 11C-epinephrine Catecholamine ⇓ 11C-hydroxyephedrine (11C-HED) Catecholamine analog ⇓⇓⇓⇓ 11C-phenylephrine ⇓⇓⇓⇓ ⇓⇓⇓⇓ 11C-isoproterenol ⇓⇓⇓⇓ ⇓⇓⇓⇓ 11C-DOPA ⇓⇓⇓⇓ ⇓⇓⇓⇓ 18F-DOPA ⇓⇓⇓⇓ ⇓⇓⇓⇓ 18F-fluorodopamine Catecholamine ⇓⇓⇓⇓ 123I-/114mIn-tyr3-octreotide Somatostatin analog Neuroenodocrine via 111In-DOTA-tyr3-octreotide ⇓⇓⇓⇓ somatostatin receptors 90Y-DOTA- tyr3-octreotide ⇓⇓⇓⇓ ⇓⇓⇓⇓ 86Y-DOTA- tyr3-octreotide ⇓⇓⇓⇓ ⇓⇓⇓⇓ 111In-/111In-DOTA-lanreotide ⇓⇓⇓⇓ ⇓⇓⇓⇓ 90Y-DOTA-lanreotide ⇓⇓⇓⇓ ⇓⇓⇓⇓ 99mTc-HYNIC-tyr3-octreotide ⇓⇓⇓⇓ ⇓⇓⇓⇓ 123I-vasoactive intestinal peptide Hormone Neuroendocrine via VIP-receptor
  • 12. 12 Sympathoadrenal Imaging PET Early imaging with short T1/2 Greater spatial resolution than MIBG/OCT 18F-FDG, 11C-epinephrine, 11C-hydroxyephedrine, 18F-DOPA and 18F-DA have been used to localize sympathomedulla neoplasms 18F-FDG 18F-FDG depicts glucose uptake and identified more metastases than either 123I-MIBG or 131I-MIBG 18F-FDG SUV did not distinguish benign from malignant pheos 18F-FDG not specific for symapthomedulla neoplasms (Shulkin, et al Radiology 1999;212:35-41)
  • 13. 13 Sympathoadrenal Imaging 18F-DOPA is a precursor to dopamine and a substrate for the norepinephrine transporter 18F-DOPA has been used to depict pheochromocytomas and other sympathomedulla tumors. Hoegerle et al. Radiology 2002;222:507-512 Hoegerle et al. Eur J Nucl Med 2003;30:689-694 Dopamine is a better substrate for NE transporter 18F-DA has depicted benign/malignant pheochromocytomas and shown tumors in patients with negative 131I-MIBG studies Pacak et al. Hypertension 2001;38:6-8 Ilias et al. J Clin Endo Metab 2003;88:4083-4087 Sympathoadrenal Imaging 11C-hydroxyephedrine (HED) is a catecholamine analog – uptake reflects catecholamine transport/storage and neuronal reuptake 11C-HED has depicted both pheochromocytomas and neuroblastomas with high sensitivity/specificity/accuracy in small numbers of patients Shulkin et al. J Nucl Med 1992;33:1125-1131 Trampal et al. Radiology 2004;230:423-428 11C-Epinephrine has been used to localize pheochromocytomas Shulkin et al. J Nucl Med 1995;36:229P 11C-5-hydroxytryptophan, a serotonin precursor has depicted carcinoid tumors and metastases to liver/lymph nodes > than CT/OCT Eriksson et al. Ann NY Acad Sci 2002;970:159-69 Trampal et al. Radiology 2004;230:423-428 Trampal et al. Radiology 2004;230:423-428
  • 14. 14 Clinical Utility of PET in the Evaluation of Adrenal Tumors Clinical Indication Radiopharmaceutical Adrenal Medulla Depicting sources of hypercatecholaminemia - intra/extra-adrenal/metastatic/familial pheo 18F-fluorodeoxyglucose, 11C-epinephrine, 11C-hydroxyephedrine, 18F-dopamine, 18F-dihydroxyphenylalanine Other neuroendocrine neoplasms - neuroblastoma, non-hypersecretory pheos 18F-fluorodeoxyglucose, 11C-epinephrine, 11C-hydroxyephedrine, 18F-dopamine, 18F-dihydroxyphenylalanine 68Ga-DOTA-octreotide Copyright ©2006 The Endocrine Society Waintrop, C. et al. J Clin Endocrinol Metab 2006;91:3271-3272 Copyright ©2006 The Endocrine Society Waintrop, C. et al. J Clin Endocrinol Metab 2006;91:3271-3272 Chen L, et. al. Clin Nucl Med 32:182-5, 2007
  • 15. 15 Copyright ©2006 The Endocrine Society de Lonlay, P. et al. J Clin Endocrinol Metab 2006;91:933-940 FIG. 3. PET images in a patient with diffuse HI Sympathoadrenal Imaging 68Ga-DOTA-D-Phe1-Tyr3-Octreotide Somatostatin analog with affinity for SSTR expressing tumors Used to depict neuroendocrine tumors in a limited number of patients Kowalski et al. Mol Imaging and Biol 2003;5:42-48. Win et al. QJNM Mol Imaging 2007 (in press). Nuclear Medicine in Endocrinology Nuclear Medicine will continue to make important contributions to the evaluation of the endocrine system using tracer kinetic principles established over the last 50 years. For the future: -Increasingly higher resolution imaging with direct anatomic correlation -New radiopharmaceuticals tailored for specific metabolic, molecular or gene-based targets

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