Society of Nuclear Medicine Procedure Guideline for Scintigraphy for Differentiated Papillary and Follicular Thyroid Cancer Authors: Edward B. Silberstein, MD, Chair (University of Cincinnati Medical Center, Cincinnati, OH); Abass Alavi, MD (Hospital of the University of Pennsylvania, Philadelphia, PA); Helena R. Balon, MD (William Beau- mont Hospital, Royal Oak, MI); David Becker, MD (Weill Cornell Medical School, New York, NY); N. David Charkes, MD (Temple University Hospital, Philadelphia, PA); Susan E.M. Clarke, MD (Guy’s and St. Thomas NHS Foundation Trust, School of Medicine, King’s College, London); Chaitanya R. Divgi, MD (Hospital of the University of Pennsylvania, Philadelphia, PA); Kevin J. Donohoe, MD (Beth Israel Deaconess Medical Center, Boston, MA); Dominique Delbeke, M.D, PhD (Vanderbilt University Medical Center, Nashville, TN); Stanley J. Goldsmith, MD (Weill Cornell Medical Center, New York, NY); Donald A. Meier, MD (William Beaumont Hospi- tal, Royal Oak, MI); Salil D. Sarkar, MD (Jacobi Medical Center, North Bronx Healthcare Network, Bronx, NY); Alan D. Waxman, MD (Cedars Sinai Medical Center, Los Angeles, CA) I. Purpose III. Examples of Clinical or Research Applications The purpose of this guideline is to assist nuclear medicine practitioners in recommending, perform- To determine the presence and extent of residual ing, interpreting, and reporting the results of ex- functioning thyroid tissue shortly post-thyroid- tended scintigraphy for differentiated thyroid cancer. ectomy and, after 131I ablation, to detect the pres- ence and location of functioning thyroid cancer, recurrences and/or metastases. II. Background Information and Definitions Scintigraphy for detection of thyroid metastasis IV. Procedure and/or residual functioning thyroid tissue consists of obtaining images of the body, 1–3 d following the The patient should be seen by the nuclear medicine oral ingestion of 131I, or 6–48 h after 123I (recogniz- physician sufficiently early to ensure the appropri- ing that the longer time period will require higher ate diagnosis has been made, the patient is suitable dosages of 123I). 18F-FDG PET may be helpful for for scintigraphy, the necessary laboratory studies patients with a rising serum thyroglobulin and nega- have been obtained, and low-iodine diet instruc- tive or minimal iodine uptake. Other radiopharma- tions have been given. This initial appointment is ceuticals such as 201Tl and 99mTc sestamibi may also important for establishing the doctor/patient rela- provide useful information. tionship. The Society of Nuclear Medicine (SNM) has written and approved these guidelines as an educational tool designed to promote the cost- effective use of high-quality nuclear medicine procedures or in the conduct of research and to assist practitioners in providing appropriate care for patients. The guidelines should not be deemed inclusive of all proper procedures nor exclusive of other procedures reasonably directed to obtaining the same results. They are neither inflexible rules nor requirements of practice and are not intended nor should they be used to establish a legal standard of care. For these reasons, SNM cautions against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment about the propriety of any specific procedure or course of action must be made by the physician when considering the circumstances presented. Thus, an approach that differs from the guidelines is not necessarily below the standard of care. A conscien- tious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in his or her reasonable judgment, such course of action is indicated by the condition of the patient, limitations on available resources, or advances in knowledge or technology subsequent to publication of the guidelines. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available re- sources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitio- ners in achieving this objective. Advances in medicine occur at a rapid rate. The date of a guideline should always be considered in determining its current applicability. 2 SCINTIGRAPHY FOR DIFFERENTIATED THYROID CANCER A. Patient Preparation 4. The sensitivity of whole-body scintigraphy 1. Avoidance of interfering materials can be improved if the patient follows a strict The concentration of radioiodine in func- low-iodine diet starting 7–14 d prior to ad- tioning thyroid tissue is affected by many ministration of the radioiodine tracer and factors such as: continuing throughout the period of imag- a. Medications, especially thyroid hormones. ing (and for a day or so after treatment). b. Iodine-containing food (eg, kelp) and B. Information Pertinent to Performing the medications (eg, iodinated contrast, Procedure amiodarone, betadine). Imaging should 1. Compliance with a low-iodine diet be delayed for a period long enough to 2. TSH level eliminate the effects of these interfering 3. History of thyroid hormone withdrawal or factors. A low-iodine diet is followed utilization of rhTSH. for 7–14 d before the radioiodine is 4. Serum thyroglobulin and anti-thyroglobulin given, as it significantly increases the antibody levels. uptake of radioiodine by functioning 5. Description of operative procedure (extent thyroid tissue. The goal is a 24-h urine of thyroidectomy) and detailed pathologic iodine output of about 50 mcg, but this findings measurement is not felt to be necessary 6. Tumor histology, including presence or ab- in most cases. sence of capsular and/or vascular invasion 2. The sensitivity of whole-body scintigraphy and lymph node involvement for detection of functioning metastases can 7. Results of other imaging procedures be optimized at TSH levels of 30 mIU/L or 8. Physical examination findings more. This is achieved by the administra- 9. History of prior 131I treatment tion of recombinant human TSH (rhTSH, 10. Results of prior radioiodine scintigraphy Thyrogen®, given as two injections of 0.9 11. History of prior administration of iodinated mg intramuscularly on each of two consecu- contrast (especially as part of a CT exami- tive days, with 4 mCi of 131I given the next nation) or iodine-containing drugs (eg, day, TSH and serum tg obtained 2 d after amiodarone) the oral 131I), or, in the near athyreotic pa- 12. Menstrual history/pregnancy test tient, by withdrawing replacement thyroid 13. Nursing/lactation history hormone therapy for 3–4 weeks. The patient 14. Surgeon performing the thyroidectomy has should be informed of the potential side ef- sufficient and ongoing expertise in perform- fects of rhTSH injection, and of hypothy- ing this procedure. roidism, if this latter course is taken. In or- C. Precautions der to avoid severely symptomatic, pro- Patients receiving more than about 5–7 mCi of 131 longed hypothyroidism, patients may be I should follow the same precautions as pa- maintained on triiodothyronine (T3) until tients treated with 131I for hyperthyroidism. 10–14 d prior to administration of the ra- D. Radiopharmaceuticals dioiodine. rhTSH will be required if the pa- 1. Oral 131I is administered in activities of 1–5 tient cannot be prepared by near-total thy- mCi or less, with many preferring a range roidectomy, in the presence of sufficient of 1–2 mCi because of data suggesting that functioning tumor to suppress endogenous stunning (decreased uptake of the therapy TSH, or with pituitary insufficiency or iso- dose of 131I by residual functioning thyroid lated TSH deficiency. tissue or tumor due to cell death or dysfunc- 3. Serum TSH level should be measured 1–3 tion caused by the activity administered for d prior to radioiodine administration. The diagnostic imaging) is less likely at the TSH level should be greater than about 30 lower activity range. However, stunning mIU/L, unless there is significant residual may not influence the outcome of treatment. functioning thyroid tissue that will prevent With higher dosages, detection of more io- an endogenous TSH elevation. Concomi- dine concentrating tissue has been reported. tant serum thyroglobulin and anti-thyro- 2. Oral 123I may be administered at a dosage globulin antibody assays should be ob- typically between 0.4–5.0 mCi, which may tained. avoid stunning. SCINTIGRAPHY FOR DIFFERENTIATED THYROID CANCER 3 3. Positron emission tomography with 18F-FDG E. Image Acquisition may be used to identify tumors that are not 1. Instrumentation visualized with radioiodine. While these tu- For 131I, a large-field-of-view camera and a mors are less likely to respond to 131I treat- high-energy parallel hole collimator is used. ment, they may be amenable to surgical resec- For 123I, 201Tl and 99mTc, a low-energy col- tion, external radiation or embolization. Tu- limator and a large-field-of-view camera are mors that are radioiodine-negative and FDG- preferred. PET/CT scanning will provide positive are associated with a less favorable the optimal imaging when 18F-FDG is em- prognosis. Imaging with FDG is more sensi- ployed. If PET/CT is performed, refrain tive when the serum TSH level is elevated, from using oral or intravenous iodinated which can be achieved with rhTSH or, less contrast agents, as this will impact potential 131 quickly, with thyroid hormone withdrawal. I treatment. 99m Tc-sestamibi, preferably with SPECT, may 2. Patient positioning be used to image radioiodine-negative metas- Lying supine on an imaging table. tases if FDG–PET is not available. 201Tl is un- 3. Imaging protocols commonly used for this purpose today. a. Post-thyroidectomy, pre-ablation choices: Radiation Dosimetry for Adults Radiopharmaceuticals Administered Organ Receiving the Effective Dose Activity Largest Radiation Dose MBq mGy/MBq mSv/MBq (mCi) (rad/mCi) (rem/mCi) 18 F-fluorodeoxyglucosea 370–740 0.16 0.019 bladder wall (10–20) (0.59) (0.07) 123 b Na I iodide 14.8–185 po 0.09 0.013 (0% thyroid uptake) bladder wall (0.4–5.0)c (0.33) (0.048) Na131I iodideb 37–185 0.81 0.11 (0% thyroid uptake) bladder wall (1–5)c (3.0) (0.41) 201 b Tl chloride 110–185 iv 0.4 6 0.16 kidney (3–5) (1.70) (0.60) 99m Tc sestamibib 370–740 iv 0.050 0.015 upper large intestine (10–20) (0.185) (0.056) a. Delbeke D, Coleman RE, Guiberteau MJ, et al. Procedure guideline for tumor imaging with 18F-FDG PET/CT 1.0. J Nucl Med 2006;47:885–895. b. International Commission on Radiological Protection. Radiation Doses to Patients from Radiopharmaceuticals. Oxford: Perga- mon Press, 1988. c. In general the larger activity of radioiodine one administers, the higher the scan sensitivity for metastatic thyroid cancer. This must be balanced with the apparent “stunning” effect described for both 123I and 131I at higher dosages, although the effect this stunning has on eventual outcome is unclear and may be minimal. The ranges for diagnostic dosages of radioiodine given in the table are wide, but all have been used successfully by thyroid cancer consultants. 4 mCi of 131I are recommended by the manu- facturer if rhTSH is employed. 4 SCINTIGRAPHY FOR DIFFERENTIATED THYROID CANCER i. rhTSH may be used to elevate the tion if regional or distant metas- serum TSH for post-operative pre- tases are detected on the pre- ablative scanning with either 123I or ablation scan. 131 I (dosages in table above) prior to iv. Post-131I ablation scintigraphy is rec- 131 I therapeutic ablation. This is an ommended 4–10 d after administering “off-label” indication for rhTSH (not the ablative dosage, as this provides in the FDA package insert), but em- enhanced sensitivity over all the pre- ployed by a number of consultants. ablative imaging procedures noted ii. Using endogenous TSH stimulation, above. SPECT or SPECT/CT may the patient may be allowed to be- improve tissue/tumor localization. come hypothyroid, minimizing b. Post-thyroidectomy, post-ablation imag- symptoms by checking the patient’s ing for restaging 6–12 months (and blood as early as three weeks post- later) post-ablation. thyroidectomy for the desired TSH i. 1–5 mCi of 131I with scanning at 1–3 level (>30 mIU/L) to optimize scan d (daily scanning required if quanti- sensitivity. tative dosimetry is employed). iii. The American Thyroid Association ii. rhTSH protocol if likelihood of 131I Guideline suggests not imaging be- therapy is low or intermediate. fore 131I therapy. Nuclear medicine iii. Endogenous TSH stimulation if consultants are divided as to the need probability of 131I therapy is high; for thyroid imaging before 131I abla- some consultants are now employing tion, but one must recognize the low rhTSH “off label” successfully for but finite frequency of significant this therapeutic purpose. clinical problems such scanning can c. 18F-FDG uncover, including the following: i. Indication: rising serum thyroglobu- (a) About 1% of the time the thyroi- lin with one post-131I therapy scan dectomy is truly total, and, if there negative. are no remnants to be ablated, (a) When there is a suspicion that then giving 131I would achieve no the 131I scan will be negative or purpose, although in high-risk pa- have low sensitivity, some con- tients treatment of occult metasta- sultants recommend simultane- ses may be warranted. ously performing a 18F-FDG (b) If too large a thyroid remnant scan (the sensitivity of which is remains post-operatively, and higher when the serum TSH is one is unaware of this, then the elevated) after rhTSH stimula- usual ablative dose, ranging from tion, on the Wednesday (day 3) about 75–150 mCi of 131I, might following rhTSH injections on uncommonly cause radiation thy- days 1 and 2, then the 131I scan roiditis with clinically significant on day 5, Friday, This saves the neck pain and swelling. cost and inconvenience of two (c) Distant metastases in the brain or sets of rhTSH injections. Simul- spinal cord might require pre- taneous 18F-FDG and 131I im- radiation corticosteroids to avoid aging are also possible after thy- complications caused by radia- roid hormone withdrawal with tion-induced swelling. resultant TSH elevation. (d) At some institutions, large thy- ii. Patient preparation requires 2 d of roid remnants, especially in high rhTSH injection to optimize sensitiv- risk patients, are removed with a ity. second thyroidectomy before 4. Timing of the Images high dosage 131I can be given, a. For 131I, images are obtained 1–3 d after as lower dosages of 131I may the radiopharmaceutical administration. fail to ablate large remnants. Later images, when background is di- (e) Larger dosages of radioiodine are minished, often provide better definition usually given at the time of abla- of low-activity lesions. Imaging 4–10 d SCINTIGRAPHY FOR DIFFERENTIATED THYROID CANCER 5 after a therapeutic dose of 131I can be G. Processing helpful in demonstrating small or func- None tioning metastases not visible with the H. Interpretation Criteria low scanning dose. An adequate physical examination and history b. For 123I, images are obtained 6–48 h fol- should be obtained. The presence of palpable lowing the administration of the radio- tissue in the neck should be defined for correla- pharmaceutical, recognizing that higher tion with the scintigraphic findings. dosages will be necessary for the longer Special attention should be paid to the pre- time period. cise placement of markers on anatomical land- c. For 18F-FDG, images are begun 60–90 marks. For appropriate interpretation of anterior min following injection. thyroid bed findings, it is necessary to be certain d. For 99mTc sestamibi and 201Tl, images of the location of the nose and/or mouth, thyroid are obtained 15 min after administration cartilage and sternal notch in the neck. For of the radiopharmaceutical. SPECT may whole-body imaging, other landmarks may be be more accurate for localization of ab- important such as costal margins, xyphoid proc- normalities. ess, pubic symphysis, and iliac crests. Posteri- 5. Image Acquisition (all tracers) orly, the location of the spine, iliac crests, etc, a. Anterior and posterior images from the can be identified and transferred to the film. In top of the skull through the femurs are addition to the scintigraphic images with mark- obtained. Spot images should be ob- ers, duplicate images should be obtained without tained for approximately 10–15 min per the markers to avoid interference with areas of view. Longer imaging times may be uptake adjacent to the markers. helpful for images obtained more than I. Reporting 3 d after administration of the radioio- The report should include a qualitative estimate dine. of the size, activity and location of any areas of b. If images are obtained with a whole- uptake that correspond to any functioning nor- body scanner, the scan speed should be mal or abnormal thyroid tissue. Particular atten- adjusted so that whole body imaging tion should be paid to activity in the thyroid takes approximately 40 min per pass or bed. Scan images cannot differentiate residual 4–5 cm/min for a dosage of 4 mCi 131I, normal thyroid tissue (ie, thyroid remnants) using a high-energy collimator. from tumor there. Comparison with prior scans c. Pinhole images of the neck for single can often be useful in defining the significance photon emitters, in combination with of localized neck activity. Lateral and oblique adequate anatomic markers and careful views may be useful in separating thyroid bed palpation, may be effective in differenti- activity from neighboring lymph node activity. ating between normal residual thyroid tis- Results of recent thyroglobulin assays may sue, salivary gland uptake, residual thy- be useful, especially in interpreting negative roid cancer, and lymph node metastasis, scintigraphic finding, recognizing that about but this is often a difficult determination. 20% of patients with thyroid cancer have anti- SPECT/CT with 131I may occasionally be bodies to thyroglobulin, which invalidate the helpful in this distinction. serum thyroglobulin measurement. d. 24-h neck iodine uptake measurements J. Quality Control are often helpful in determining the mass See Society of Nuclear Medicine Guideline on of remaining thyroid tissue or tumor. General Imaging. e. SPECT or SPECT/CT may be helpful to K. Sources of Error improve tissue localization 1. Local contamination (clothing, skin, hair, F. Interventions collimator, imaging table) Giving the patient an apple or crackers to chew 2. Esophageal activity and swallow is more useful than a drink of wa- 3. Asymmetric salivary gland uptake ter to eliminate common artifacts from mouth 4 Breast uptake and esophageal activity. 5. Thymus uptake 6 SCINTIGRAPHY FOR DIFFERENTIATED THYROID CANCER V. Issues Requiring Further Clarification E. Iwata M, Kasagi K, Misaki T et al. Comparison of whole-body 18F-FDG PET, 99mTc-MIBI A. What is the best dose of 131I for whole-body SPET, and post-therapeutic 131I-Na scintigra- imaging that would provide the most diagnostic phy in the detection of metastatic thyroid can- information with minimal stunning (see section cer. Eur J Nucl Med Mol Imaging IV.D.1. above) both in the initial work-up and 2004;31:491–498. to detect recurrences? F. Lakshmanan M, Schaffer A, Robbins J, et al. A B. What are the detrimental long term affects, if simplified low-iodine diet in I-1 scanning and any, of thyroidal stunning? therapy of thyroid cancer. Clin Nucl Med C. What is the role, and adequate minimal dosage, 1988;13:866–868. of 123I in whole-body surveys post-thyroid- G. Palmedo H, Bucerius J, Joe A. Integrated ectomy and pre-ablation, and possibly for me- PET/CT in the differentiated thyroid cancer: tastatic disease, compared to 131I? Diagnostic accuracy and impact on patient D. Does lithium administration promote retention management. J Nucl Med 2006;47:616–624. of radioiodine in metastatic foci sufficiently to H. Park HM, Park YH, Zhou XH. Detection of be of therapeutic value? thyroid remnant/metastases without stunning: E. What is the role of radioiodine scanning after an ongoing dilemma. Thyroid 1997;7:277–280. surgery and before ablation? I. Plotkin M, Hautzel H, Krause BJ, et al. Impli- F. What is the role of somatostatin receptor agents cation of 2-18fluoro-2-deoxyglucose positron in detecting thyroid cancer when the serum thy- emission tomography in the follow-up of roglobulin is elevated but the 131I and 18F-FDG Hurthle cell thyroid cancer. Thyroid 2002;12: scans are negative? 155–161. G. Does the sensitive serum thyroglobulin assay J. Sarkar SD, Kalapparambath TP, Palestro CJ. allow the nuclear medicine physician to use Comparison of 123I and 131I for whole-body im- only 1–2 mCi of 131I for the detection of thyroid aging in thyroid cancer. J Nucl Med 2002;43: cancer, rather than higher, potentially stunning 632–634. dosages, since sensitivity of this dosage is K. Sherman SI, Tielens ET, Sostre S, et al. Clini- lower than one would see using 5 mCi? cal utility of post-treatment radioiodine scans H. What is the value of administering ablative dos- in the management of patients with thyroid ages of 131I when the post-thyroidectomy scan carcinoma. J Clin Endocrinol Metab 1994;78: and serum thyroglobulin are negative in a high- 629–634. risk patient? L. Shiga T, Tsukamoto E Nakada K, et al. Com- parison of 18F-FDG, 131I-Na, and 201Tl in diag- VI. Concise Bibliography nosis of recurrent or metastatic thyroid carci- noma. J Nucl Med 2001;42:414–419. A. Chin BB, Patel P, Cohade C, et al. Recombi- M. Sisson JC. Selection of the optimal scanning nant human thyrotropin stimulation of fluoro- agent for thyroid cancer. Thyroid 1997;7(2): D-glucose positron emission tomography up- 295–302. take in well-differentiated thyroid carcinoma. J N. Wang WW, Larson SM, Fazzari M, et al. Prog- Clin Endocrinol Metab 2004;89:91–95. nostic value of [18F] fluorodeoxyglucose posi- B. Cooper DS, Doherty GM, Haugen BR, et al. tron emission tomographic scanning in patients The American Thyroid Association: Manage- with thyroid cancer. J Clin Endocrinol Metab ment guidelines for patients with thyroid nod- 2000;85:1107–1113. ules and differentiated thyroid cancer. Thyroid O. Yen TC, Lin HD, Lee CH, et al. The role of 2006;16:1–33. technetium-99m-sestamibi whole-body scans in C. Dam HQ, Kim SM, Lin HC, et al. 131I therapeu- diagnosing metastatic Hurthle cell carcinoma of tic efficacy is not influenced by stunning after the thyroid gland after total thyroidectomy: a diagnostic whole body scanning. Radiology comparison with iodine-131 and thallium-201 2004;232:527–333. whole-body scans. Eur J Nucl Med 1994;21: D. de Geus-Oei L, Oei H-Y, Hennemann G, et al. 980-983. Sensitivity of 123I whole-body scanning and thyroglobulin in the detection of metastases or recurrent differentiated thyroid cancer. Eur J Nucl Med 2002;29:768–774.
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