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 < CT High spatial resolution, no radiation, tissue characterization Radio-frequency signal by protons in magnetic field Magnetic Resonance ++++ Widely employed radiation 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 utility Limited resolution, interference by fat and bowel gas Widely available, no radiation exposure Reflection of ultrasound depicts anatomy Ultrasound Relative Cost Comments Disadvantages Advantages Underlying Principal Technique 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.
Transcript
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
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 & adjuvant colon cancer s/p surgery & adjuvant chemoTxchemoTx, evaluation of , evaluation of
rising CEA.rising CEA.
thyroidthyroid
thyroid
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 lymphoma grade 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’’s s thyroiditisthyroiditis, s/p (R) , s/p (R)
thyroid thyroid 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 scans18F-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 papillary llary
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 scan I scan
10/0110/01
81 81 y/oy/o manman
* Papillary thyroid ca s/p resection 1992 followed by * Papillary thyroid ca s/p resection 1992 followed by 131131I I TxTx
* Extensive liver * Extensive liver metsmets since 1997since 1997Robbins, 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
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
Recurrent Recurrent metastaticmetastatic HurthleHurthle cell ca: 57 y/o male with cell ca: 57 y/o male with HxHx treated treated HurthleHurthle
cell ca x 3 yrs. cell ca x 3 yrs. ↑↑TG, suspected R ant rib metastasis confirmed on TG, suspected R ant rib metastasis confirmed on 111111InIn--
Octreoscan and FDGOctreoscan and FDG--PET (curved arrow) which was PET (curved arrow) which was resectedresected. FDG. FDG--PET PET
detected an additional abnormal focus in the thyroid bed not seedetected an additional abnormal focus in the thyroid bed not seen on the n 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 for 56 y/o man previously treated for medullarymedullary thyroid cancer now thyroid cancer now
with with ↑↑ calcitonincalcitonin..
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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
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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 involvementThyroid bed
Neck
No. patientsSPECT/CT characterizationPlanar findingsRegion 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
Parathyroid Imaging99mTc-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
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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
Greater spatial resolution than MIBG/OCT18F-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-MIBG18F-FDG SUV did not distinguish benign from malignant pheos18F-FDG not specific for symapthomedulla neoplasms
(Shulkin, et al Radiology 1999;212:35-41)
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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
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Clinical Utility of PET in the Evaluation of Adrenal Tumors
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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