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5/8/2015 Nuclear Medicine Imaging of Thyroid Cancer Jolanta M. Durski, MD Mayo Clinic Rochester MN DISCLOSURE Relevant Financial Relationship(s) None Off Label Usage PET tracers which are not FDA approved yet 1 5/8/2015 I will talk about: • Whole body radioiodine scan for DTC: • When to do it: prior to ablation, post therapy, follow up • How to do it: • Radiopharmaceuticals: I-131 versus I-123 (physical properties, cost, • • Imaging: whole body, image acquisition, processing, SPECT/CT, Patient preparation (including rhTSH use) stunning, dose etc.) • PET/CT for thyroid cancer • 18F-FDG • • • PET/CT Principles, patient preparation (? rhTSH), cost & reimbursement Use for Differentiated Thyroid Cancer, Anaplastic, Hurthle cell, Medullary & Thyroid Lymphoma Incidental thyroid uptake on FDG-PET • Other non FDA approved PET tracers • • • I-124 PET/CT F18-Fdopa, Ga68-octreotide Whole Body Radioiodine Scans at Mayo Clinic in Rochester MN ÿ 150 diagnostic whole body scans per year ÿ 50 post-treatment scans Decreasing trend reflects a change in guidelines – no remnant ablation in low risk patients 2 5/8/2015 Radioiodine Scan for Differentiated Thyroid Cancer When to do it? When to do radioiodine scan Radioiodine Scan Prior to Remnant Ablation To do or not to do? That is the question 3 5/8/2015 When to do radioiodine scan Radioiodine Scan Prior to Remnant Ablation SNMMI: YES! ATA: if expected to change management! • • • • No remnant – no need for remnant ablation Large remnant – risk of radiation thyroiditis - surgery or smaller dose Neck nodal metastases – surgery, alcohol ablation, increased dose Distant metastases – larger dose, dosimetry, steroids for CNS met, possibly local treatments • Occasional unexpected uptake e.g. breasts – postpone therapy The utility of radioiodine scans prior to iodine 131 ablation in patients with well-differentiated thyroid cancer. Van Nostrand D, Aiken M, Atkins F, Moreau S, Garcia C, Acio E, Burman K, Wartofsky L.Thyroid. 2009 . 355 sets of scans 55% of patients had findings that might have altered the management prior to ablation. When to do radioiodine scan Radioiodine Scan Prior to Remnant Ablation • 34 y/o man with papillary thyroid cancer metastatic to neck nodes, underwent thyroidectomy and bilateral neck dissection • Additional bilateral neck nodes seen on the pre-ablation scan • Additional surgery & 131I dose increased to 200 mCi 4 5/8/2015 When to do radioiodine scan Radioiodine Scan Prior to Remnant Ablation • 28 year old woman with papillary thyroid cancer, post near-total thyroidectomy • Radioiodine uptake 0.1 % • Radioiodine remnant ablation was cancelled after scan When to do radioiodine scan Post-therapy 131I Scan recommended by ATA More lesions than diagnostic I-131/I-123 scan 13% of scans, 9% change in management* *Are posttherapy radioiodine scans informative and do they influence subsequent therapy of patients with differentiated thyroid cancer? Fatourechi V, Hay ID, Mullan BP, Wiseman GA, Eghbali-Fatourechi GZ, Thorson LM, Gorman CA. Thyroid. 2000 (117 patients) usually not enough uptake for I-131 treatment** Clinical outcomes following empiric radioiodine therapy in patients with structurally identifiable metastatic follicular cellderived thyroid carcinoma with negative diagnostic but positive post-therapy 131I whole-body scans. Sabra MM, Grewal RK, Tala H, Larson SM, Tuttle RM. 2 to 10 days after treatment (ATA guideline) • Tumor to background increases with time (clearance from other tissues) • Variable effective half life in cancer tissue (0.7 to 7days***) **Determining the appropriate time of execution of an I-131 post-therapy whole-body scan: comparison between early and late imaging. Salvatori M, Nucl Med Commun. 2013 (134 patients) 3d scan more info in 7.5% of patients 7d scan more info 12% of patients*** 5 5/8/2015 When to do radioiodine scan Follow up Diagnostic Whole Body Radioiodine Scan (after remnant ablation) When evidence of recurrent disease: elevated Thyroglobulin, anti-Tg antibody, evidence of mets on other imaging or post ablation scan, high risk of persistent disease etc…. Not indicated: low risk or intermediate risk patients with undetectable Tg on replacement, negative anti Tg ab and negative US (ATA guidelines) ……..more details later in this session…… radioiodine scan examples Whole Body Radioiodine Scan Papillary thyroid cancer metastases 26 y/o woman with papillary thyroid cancer 8 yrs after thyroidectomy Multiple surgeries for nodal disease. Rising thyroglobulin (14) Tx 100 mCi 123I anterior Diagnostic scan posterior 4 days post therapy scan anterior posterior Additional lesions in the neck and lungs on the post treatment scan 6 5/8/2015 radioiodine scan examples Whole Body Radioiodine Scan Papillary thyroid cancer metastases 29 y/o man presented with stridor, slowly growing large thyroid mass. Thyroidectomy, bilateral lateral neck dissection August 2011. 305 mCi I-131(with rhTSH) Sept 2011 Liver uptake Physiologic on post tx scan 123I Diagnostic scan Sept 2011 Thyroglobulin 78 5 days post therapy Diffuse lung uptake Tiny (up to 3 mm) nodules on CT Follow up scan June 2013 Thyroglobulin 2.6 radioiodine scan examples WB 123I scan - Skeletal Metastases follicular thyroid cancer • 56 y/o woman presented in 2012 with skeletal mets from follicular thyroid cancer. • History of lobectomy for goiter. Completion of thyroidectomy Aug 2012. No malignancy ever found in thyroid. • Treatment with 300 mCi with Thyrogen Oct 2012 • External radiation to left humerus and T12 Diagnostic 123I scan : Follow up 123I scan : April 2014 doing well no evidence of recurrence Tg 0.6 no ab Oct 2012 Thyroglobulin 894 March 2013 Thyroglobulin 0.6 7 5/8/2015 Radioiodine Scan for Differentiated Thyroid Cancer How to do it? How to do radioiodine scan Iodine 123 versus Iodine 131 Only 20% of I-131 gamma rays are stopped by standard gamma camera crystal versus 100% for I-123 I-123 γ energy 159 keV (good) I-131 γ energy 364 keV (too high) 8 5/8/2015 How to do radioiodine scan Iodine 123 versus Iodine 131 I-131 3% - 5% septal penetration (high energy collimator) only 0.1 – 0.3 % for I-123 This effect is most visible when there is a point source, much hotter than other areas in the field of view I-123 γ energy 159 keV (good) I-131 γ energy 364 keV (too high) How to do radioiodine scan Iodine 123 versus Iodine 131 Superiority of iodine-123 compared with iodine-131 scanning for thyroid remnants in patients with differentiated thyroid cancer. Mandel SJ, et al Clin Nucl Med. 2001 9 5/8/2015 How to do radioiodine scan Iodine 123 versus Iodine 131 No β radiation β radiation Half life 13 hours Half life 8 days Lower dose to the patient Higher dose to the patient However, longer half life allows for dosimetry Cost $306 per 2 mCi Cost $114 per 2 mCi (including $100 delivery) (including $100 delivery) Stunning is more likely How to do radioiodine scan Stunning ? Diagnostic dose of 131I prevents accumulation of the therapeutic dose Diagnostic scan Post therapy Lower dose of 131I (2 mCi) Demonstrated in a study of cultured thyroid cells* Stunning of iodide transport by (131)I irradiation in cultured thyroid epithelial cells. Postgård P et al. J Nucl Med. 2002 Reduced iodide transport (stunning) and DNA synthesis in thyrocytes exposed to low absorbed doses from 131I in vitro. Lundh C et al. J Nucl Med. 2007 Iodine transport was reduced at 0.15 Gray (50% reduction at a 3 Gray dose) equivalent to doses after diagnostic scans. DNA measurement showed reduction in cell numbers at 8 Gy 10 5/8/2015 How to do radioiodine scan Is There Stunning After 123I ? Yes, but less than with 131I * Radiation-induced thyroid stunning: differential effects of (123)I, (131)I, (99m)Tc, and (211)At on iodide transport and NIS mRNA expression in cultured thyroid cells. Lundh C, et al. J Nucl Med. 2009 stunning effect per unit of absorbed dose is more severe with 123I than 131I * (about 2x) (internal conversion followed by Auger electrons) However, the absorbed dose is about 100 x higher with 131I** (the difference may be smaller for small metastatic lesions) ** Biokinetics of iodide in man: refinement of current ICRP dosimetry models. Johansson L et al. Cancer Biother Radiopharm. 2003 How to do radioiodine scan Radioiodine Scan Dose and Image Acquisition Iodine-123 1.5 – 3 mCi (ATA guideline) Iodine 131 1 – 3 mCi (ATA guideline) SNMMI up to 5 mCi (Mayo 5mCi) Whole body image at 24h Whole body image at 48h Medium energy collimator High energy collimator 11 5/8/2015 How to do radioiodine scan Radioiodine Scan Image Processing • Uptake in the neck • Uptake in the metastatic lesions • Whole body retention How to do radioiodine scan SPECT/CT more accurate than planar imaging • remnant thyroid tissue versus nodes • physiological uptake versus metastases At Mayo routine neck & upper thorax, additional areas as needed • Salivary, GI, Lacrimal uptake • Contamination artifacts • detects more metastatic lesions • better localization of metastases • fewer additional tests & mistakes Value of ¹³¹I SPECT/CT for the evaluation of differentiated thyroid cancer: a Xue YL, Qiu ZL, Song HJ, Luo QY. Eur J Nucl Med Mol Imaging. 2013 systematic review of the literature. 1066 patients Incremental diagnostic value over planar imaging in 48% to 88% of patients Modification of therapeutic strategies in 25% of patients 12 5/8/2015 SPECT/CT SPECT/CT Physiologic 123I Uptake in the Esophagus SPECT/CT SPECT/CT Lingual Remnant and Tissue in the Thyroglossal Tract 13 5/8/2015 SPECT/CT 123I SPECT/CT Thyroid Remnant SPECT/CT 123I SPECT/CT Residual Thyroid Tissue and Lymph Node Metastasis Uptake in the neck 3.3% 14 5/8/2015 SPECT/CT 123I SPECT/CT Recurrent Differentiated Thyroid Cancer Normal uptake in hiatal hernia SPECT/CT Radioiodine Avid Mediastinal Metastases 123I SPECT/CT Thyroglobulin 332 decreased to 22 after 150 mci 15 5/8/2015 SPECT/CT Radioiodine Avid Pulmonary Metastases 123I SPECT/CT SPECT/CT 123I SPECT/CT Skull Metastasis salivary pooling After 131-I Tx 16 5/8/2015 How to do radioiodine scan Radioiodine Scan Patient Preparation • Low Iodine diet • wait 6-8 weeks post iodinated iv contrast • Pt not lactating (stop for 6 weeks, diagnostic scan helpful), • not pregnant • Thyroid hormone withdrawal (TSH goal 30) • RhTSH How to do radioiodine scan rhTSH Prior to Radioiodine Scan Mayo Clinic Rochester Thyroid Hormone Withdrawal Patients can avoid symptoms of hypothyroidism Thyrogen Faster renal clearance! decreased dose to the patient with subsequent remnant ablation Cost: $1,381 per box (2 vials) • Most useful for • Patients that can not tolerate withdrawal • Patients unable increase endogenous TSH: • Large remnant • Pituitary insufficiency 17 5/8/2015 How to do radioiodine scan rhTSH Scan Protocol Mayo Rochester protocol for rhTSH stimulated scan & remnant ablation Protocol: rhTSH IM day 1 & 2 Day 1 scan dose day 3 rhTSH Day 2 rhTSH Day 3 Day 4 123I 5 mCi scan rhTSH 131I Therapy The effects last longer than the blood concentration levels How to do radioiodine scan Is radioiodine scan more sensitive with THW versus rhTSH ? *Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma. Ladenson PW et al N Engl J Med. 1997 ** Recombinant human thyroid-stimulating hormone versus thyroid hormone withdrawal in the identification of metastasis in differentiated thyroid cancer with 131I planar whole-body imaging and 124I PET. Van Nostrand D et al J Nucl Med. 2012 ***Preparation by recombinant human thyrotropin or thyroid hormone withdrawal are comparable for the detection of residual differentiated thyroid carcinoma. Robbins RJ, Tuttle RM, Sharaf RN, Larson SM, Robbins HK, Ghossein RA, Smith A, Drucker WD.J Clin Endocrinol Metab. 2001 Prospective study, 127 pts Withdrawal more sensitive* Significantly more foci of metastases of DTC may be identified in patients prepared with THW than in patients prepared with rhTSH.** No difference in diagnostic accuracy*** Probably reduced uptake due to faster blood clearance with RhTSH, (dose to the patient lower too), this could be compensated by using I-123 ****Iodine biokinetics and dosimetry in radioiodine therapy of thyroid cancer: procedures and results of a prospective international controlled study of ablation after rhTSH or hormone withdrawal. Hänscheid H et al J Nucl Med. 2006 effective half-life in the thyroid tissue significantly longer after rhTSH than during hypothyroidism**** 18 5/8/2015 Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. …….more details later in this session…… Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA, Ricarte-Filho JC, Domínguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA. N Engl J Med. 2013 PET/CT for Thyroid Cancer Imaging of locally recurrent and metastatic thyroid cancer with positron emission tomography. Conti PS, Durski JM, Bacqai F, Grafton ST, Singer PA. Thyroid. 1999 19 5/8/2015 PET/CT Principles of PET/CT - + Positron is Beta (+) particle, Annihilates with electron Two gamma rays 511 keV in opposite directions Better resolution 4-5 mm (SPECT 8-10 mm) Positron emitters are often isotopes of elements naturally present in the body (C,N,F,O) 39 PET/CT F-18 Fluorodeoxyglucose 18F - FDG Accumulates in malignant cells • Increased metabolism & Warburg effect Otto Warburg found in 1924 that cancer cells tend to “ferment” glucose into lactate even in the presence of sufficient oxygen to support mitochondrial oxidative phosphorylation. Malignant cells typically have glycolytic rates up to 200 times higher than those of their normal tissues of origin F18-FDG - 2-Deoxy-2-fluoro-D-glucose • FDG is Phosphorylated in the cells, but not metabolized further • Not re-absorbed in kidneys (good for imaging) • Accumulates in inflammation 40 20 5/8/2015 PET/CT FDG Normal Distribution Brain - intense uptake Thyroid – low uptake Heart - variable uptake Urinary tract - intense uptake Liver SUV 3 Mediastinal blood pool 2.5 SUV = standard uptake value radioactivity concentration in a selected part of the body radioactivity concentration in the hypothetical case of an even distribution throughout the whole body PET/CT 18F-FDG PET/CT Patient Preparation Fasting for 4 - 6 hours No insulin for 4 hours Insulin will cause diffuse muscle uptake Glucose level < 200 mg/dl Glucose competes with labelled glucose Good hydration to help clear the tracer from the background No vigorous exercise for 24 hours to avoid muscular uptake 21 5/8/2015 PET/CT 18F-FDG PET/CT for Differentiated Thyroid Cancer Evaluation for residual or recurrent disease in patients with Elevated Thyroglobulin & negative radioiodine scan Less differentiated cancer = glucose metabolism 17 studies 571 patients DTC & negative radioiodine scan* Patient based sensitivity 84% specificity 84% Lesion based sensitivity 92% specificity 78% Best when stimulated TG >10 ng/ml** ATA recommended cut off iodine uptake *Value of 18F-FDG-PET/PET-CT in differentiated thyroid carcinoma with radioiodine-negative whole-body scan: a meta-analysis. Dong MJ et al. Nucl Med Commun. 2009 **Role of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography in patients affected by differentiated thyroid carcinoma, high thyroglobulin level, and negative ¹³¹I scan: review of the literature. Bertagna F et al. Jpn J Radiol. 2010. PET/CT Papillary Thyroid Cancer Iodine Negative 18F-FDG PET/CT Positive Bone scan 123I scan 18F-FDG PET 22 5/8/2015 PET/CT Metastatic Papillary Thyroid Cancer F18-FDG PET/CT Radioiodine scan PET/CT F18-FDG PET/CT Same patient imaged 3 days apart: FDG PET/CT High FDG uptake in a metastatic jugular chain LN right side. 131I salivary radioiodine excretion post-therapy SPECT/CT No 131I uptake in the LN Slide from Trond Velde Bogsrud, MD, PhD Oslo University Hospital, Oslo, Norway, & Aarhus University Hospital, Aarhus, Denmark 23 5/8/2015 PET/CT High uptake of both 131I and FDG in a metastatic LN right lower neck Slide from Dr. Trond Velde Bogsrud High uptake of both 131I and FDG in metastasis in the left kidney PET/CT 18F-FDG PET/CT for DTC High jugular chain LNs metastases are not well seen on US Case from Dr. Trond Velde Bogsrud 24 5/8/2015 PET/CT 18F-FDG PET/CT for Thyroid Cancer May be used regardless of Radioiodine scan result Prognostic information* *Real-time prognosis for metastatic thyroid carcinoma based on 2-[18F]fluoro-2-deoxy-D-glucose-positron emission tomography scanning. Robbins RJ, Wan Q, Grewal RK, Reibke R, Gonen M, Strauss HW, Tuttle RM, Drucker W, Larson SM. J Clin Endocrinol Metab. 2006 (400 patients with thyroid cancer of follicular origin followed for median of 7.9 years, 221 positive metastases on initial PET) • FDG positive metastases = much higher mortality (7x)* • aggressiveness of therapy should match the FDG-PET status* Used at Mayo to guide therapy choice for recurrent neck disease • (surgery vs alcohol ablation vs radiation vs observation) • especially for aggressive histology & after multiple surgeries PET/CT 18F-FDG PET/CT for DTC Initial staging of high risk patients Post-thyroidectomy assesment of DTC with agressive histology* *Postoperative fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography: an important imaging modality in patients with aggressive histology of differentiated thyroid cancer. Nascimento C, Borget I, Al Ghuzlan A, Deandreis D, Hartl D, Lumbroso J, Berdelou A, Lepoutre-Lussey C, Mirghani H, Baudin E, Schlumberger M, Leboulleux S.Thyroid. 2015 Apr (38 consecutive patients with aggresive histology of DTC, FDG PET/CT within 3 months of post-ablation scan) • Metastases found in 53% of patients • PET/CT more sensitive than post tx radioiodine scan* • suggested routine use in patients with aggressive histology* 25 5/8/2015 PET/CT Medicare Reimbursement of 18F-FDG-PET-CT for Thyroid Cancer 2013 Change 1 PET/CT initial staging plus 3 subsequent scans Current pricing: Whole body PET/CT Nominal: $6,536.83 Medicare: $1,565.44 FDG Nominal: $241.00 Medicare: $96 http://www.cancerpetregistry.org/pdf/ FinalNOPR-PET-Webinar-6-19-2013.pdf PET/CT 18F-FDG PET/CT for DTC Role of Recombinant TSH rhTSH used in PET 44% of time (TG positive radioiodine negative patients) Survey of 288 ATA members • Detects more lesions (Odds Ratio 4.9)* • Detects more patients with true positive lesions (OR 2.5)* • Better target to background* • Change of management 9%* • More sensitive for lesion detection (95 vs 81%) • More sensitive for detection of involved organs (94 vs 79%) • Not significantly different detection of patients (with any lesions) 7 prospective trials 168 patients *The role of TSH for 18F-FDG-PET in the diagnosis of recurrence and metastases of differentiated thyroid carcinoma with elevated thyroglobulin and negative scan: a meta-analysis. Ma C et al.Eur J Endocrinol. 2010 ** Assessment of the incremental value of recombinant thyrotropin stimulation before 2-[18F]-Fluoro-2-deoxy-Dglucose positron emission tomography/computed tomography imaging to localize residual differentiated thyroid cancer. Leboulleux S et al. J Clin Endocrinol Metab. 2009 largest trial 63 patients Most useful when: normal neck & chest CT scan & normal neck US & elevated, but not vey high TG Reimbursement (negative radioiodine scan has to be documented) Forms at Genzyme website: http://www.thyrogen.com/patients/TreatingwithThyrogen/ThyrogenCoverage/ThyrogenONE.aspx 26 5/8/2015 PET/CT 18F-FDG PET/CT for Thyroid Cancer Mayo Clinic in 2013 PET/CT PET/CT F18-FDG Anaplastic Thyroid Cancer • Very sensitive • Useful for • Evaluation for metastases (especially skeletal) • Surgical planning • Radiation therapy planning • Evaluation of treatment response • Changed management in 50% * *18F-FDG PET in the management of patients with anaplastic thyroid carcinoma. Bogsrud TV, Karantanis D, Nathan MA, Mullan BP, Wiseman GA, Kasperbauer JL, Reading CC, Hay ID, Lowe VJ. Thyroid. 2008 27 5/8/2015 PET/CT PET/CT F18-FDG Anaplastic Thyroid Cancer PET/CT 18F-FDG PET/CT Hurthle Cell Carcinoma • Intense FDG uptake • Poor radioiodine accumulation • 18F-FDG PET/CT very accurate (sens. 96% spec.95%)* *Diagnostic accuracy and prognostic value of 18F-FDG PET in Hürthle cell thyroid cancer patients. Pryma DA, Schöder H, Gönen M, Robbins RJ, Larson SM, Yeung HW. J Nucl Med. 2006 28 5/8/2015 PET/CT 18F-FDG PET/CT Hurthle Cell Carcinoma history of Hürthle cell cancer complaint of diffuse aches. CT indeterminate lung nodule with some mediastinal adenopathy, US and 131I scans negative. PET image showed widespread bone and lung metastases, confirmed with right hilar biopsy. 18F-FDG PET of patients with Hürthle cell carcinoma. Lowe VJ, Mullan BP, Hay ID, McIver B, Kasperbauer JL. J Nucl Med. 2003 PET/CT 18F-FDG PET/CT for Medullary Thyroid Cancer Suspected residual or recurrent MTC Useful if calcitonin ≥ 1,000 ng/L Pooled detection rate 75 % * *Detection rate of recurrent medullary thyroid carcinoma using fluorine-18 fluorodeoxyglucose positron emission tomography: a meta-analysis. Treglia G, et al. Endocrine. 2012 Low sensitivity if calcitonin < 1,000 FDG positive disease has worse prognosis** Liver Metastasis **The prognostic value of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography in patients with suspected residual or recurrent medullary thyroid carcinoma. Bogsrud TV, Karantanis D, Nathan MA, Mullan BP, Wiseman GA, Kasperbauer JL, Reading CC, Björo T, Hay ID, Lowe VJ. Mol Imaging Biol. 2010 Sensitivity better for sporadic or familial MTC, Worse for MEN2A*** *** Role of [(18)F]FDG-PET/CT in the detection of occult recurrent medullary thyroid cancer. Skoura E, et al. Nucl Med Commun. 2010 29 5/8/2015 PET/CT 18F-FDG PET/CT Medullary Thyroid Cancer Skeletal Metastases Calcitonin level 9691 pg/ml PET/CT F18-FDG PET/CT Lymphoma Involving Thyroid • 66 y/o man came to Mayo in Aug 2013 with 12-18 month hx. of enlarging goiter. Bx Oct 2012 chronic thyroiditis. • FNA 8/22/13 Hashimoto thyroiditis. Core needle biopsy: T cell lymphoma (very rare pathology) • FDG PET/CT 8/23/13. Suspicious for lymphoma or anaplastic thyroid cancer with nodal involvement. FDG-PET/CT is routinely used for initial staging of lymphomas and evaluation of response to therapy 30 5/8/2015 PET/CT Incidental Thyroid Uptake of F18-FDG (about 4% of PET/CT scans) • Diffuse • Incidence 0.1% - 4.5%, mean 1.9% • usually represents Hashimoto thyroiditis ~ 85%*, occasionally Graves’ disease*, 4% malignancy** • Focal • Incidence 0.1% - 4.8%, mean 2.0% in Asia • 10%- 65%, mean 36% malignant ** (24% to 74%) • Higher SUV in malignant (large overlap) • Benign SUV 4.8 (3.1 SD) • Malignant SUV 6.9 (4.7 SD) *Clinical significance of diffusely increased 18F-FDG uptake in the thyroid gland. Karantanis D, Bogsrud TV, Wiseman GA, Mullan BP, Subramaniam RM, Nathan MA, Peller PJ, Bahn RS, Lowe VJ. J Nucl Med. 2007 **Risk of malignancy in thyroid incidentalomas detected by 18F-fluorodeoxyglucose positron emission tomography: a systematic review. Soelberg KK, Bonnema SJ, Brix TH, Hegedüs L. Thyroid. 2012 (125,000 subjects) PET/CT Incidental Thyroid Nodule (ITN) ACR Recommendation ITN on CT, MRI or ultrasound (no suspicious imaging features, normal life expectancy) • - further evaluation with dedicated thyroid ultrasound only if: • Nodule ≥1 cm in a patient age <35 yrs. • Nodule ≥1.5 cm in a patient age ≥35 yrs. Focal metabolic activity in the thyroid on 18FDG-PET - both dedicated thyroid ultrasound and FNA of the PET-avid lesion (if normal life expectancy) Focal activity in the thyroid on other nuclear med. studies - ultrasound Managing Incidental Thyroid Nodules Detected on Imaging: White Paper of the ACR Incidental Thyroid Findings Committee Hoang JK et al. J Am Coll Radiol. Nov. 2014 31 5/8/2015 PET/CT Incidental Thyroid F18-FDG Uptake 2014 ATA guideline: Diffuse uptake ÷ TSH & US to ensure that there s no clinically evident nodularity” Focal uptake ÷ TSH • Low TSH radioiodine thyroid scan & uptake • Normal or high TSH US, clinical evaluation and FNA PET/CT Future PET/CT Radiopharmaceuticals Available in Europe and as a research tool in some US institutions Not FDA approved for routine use Require IND application to FDA 32 5/8/2015 PET/CT Iodine-124 131I 124I Positron Emitting Radioiodine Van Nostrand D • Better resolution of PET vs SPECT • 2 X PET 4-5 mm SPECT 8-10 mm Thyroid. 2010; 20: 879-83. • Not as good as F-18 High energy of positrons 2.1 MeV (23% abundance) mean range in tissue about 3.5 mm (compared to 0.6 mm for F18) High energy gamma photon (90% abundance) • Allows for lesion dosimetry, • better quantitation of uptake with PET & half life 4.2 days • Not FDA approved for routine use • Clinical trial use of the product requires filing of an investigator-sponsored Investigational New Drug (IND) application to the FDA. • Can be produced in cyclotron, but is volatile and contaminates cyclotron • Can be ordered from IBA molecular PET/CT F18-DOPA - Best Radiopharmaceutical for Medullary Thyroid Cancer • F18-Dopa (6-L-F18-fluorodihydroxyphenylalanine) • Precursor of dopamine and other catecholamines • • • up-regulation of amino acid transporters for large amino acids like phenylalanine and tyrosine affinity for amino acid decarboxylase accumulation in monoamine storage vesicles • Used in brain research studies & • neuroendocrine tumors & congenital hyperinsulinism Not FDA approved for routine use in US requires IND application to FDA 33 5/8/2015 PET/CT PET/CT Imaging of the Medullary Thyroid Cancer • 18F-FDOPA - best radiopharmaceutical (Not FDA approved) significant diagnostic performance if Calcitonin>150 pg/mL. * • In negative FDOPA, FDG should be the next PET radiopharmaceutical, especially if Calcitonin and CEA levels are rising rapidly.* . • PET with a somatostatin analogue labelled with gallium-68 when neither FDOPA nor FDG PET are conclusive. * (Not FDA approved) • Bone scintigraphy could complement FDG PET/CT if FDOPA is not available* What is currently the best radiopharmaceutical for the hybrid PET/CT detection of recurrent medullary thyroid carcinoma? Slavikova K et al. Curr Radiopharm. 2013 Jun 6;6(2):96-105. Review PET/CT MTC (Calcitonin 260 pg/mL) FDG FDOPA For well differentiated, metastatic MTC FDOPA is the best radiopharmaceutical for PET/CT Slide from Trond Velde Bogsrud, MD, PhD Oslo University Hospital, Oslo, Norway, & Aarhus University Hospital, Aarhus, Denmark 34 5/8/2015 PET/CT Gallium 68-octreotide PET/CT SPECT 68Ga for PET/CT imaging 111 In for SPECT imaging DOTA or DTPA a chemical link between the peptide and the radionuclide NET – unknown primary Gabriel, M., et al., JNM 2007 Somatostatin analogue Much better resolution than In111-Octreotide Gallium 68 - positron emitter • Mean positron range in tissue 2.24 mm (not ideal) • Half life 68 min • Comes from Ge-68/Ga-68 Generator (made in Germany and Russia) Parent 68Ge half life - 271 days PET/CT Ga68-octreotide • Not FDA approved for routine use, requires IND • Used for medullary cancer in Europe, but FDOPA better • May have increased role when Lu177- octreotide approved for therapy in US (current multicenter phase III trial) • Medullary thyroid cancer - somatostatin avidity prior to therapy • Differentiated thyroid cancer - somatostatin avidity *Differentiated thyroid cancer: a new perspective with radiolabeled somatostatin analogues for imaging and treatment of patients. Versari A, et al.Thyroid. 2014. SSTR imaging provided positive results in more than half of the cases with radioiodine- negative DTC, and about one third ofpatients were eligible for PRRT* TG positive Radioiodine scan negative patient with papillary thyroid cancer** **Kundu P et al Eur J Nucl Med Mol Imaging 2014; 41: 1354-1362. 35 5/8/2015 36