Thyroid Remnant Dose: ¹²⁴I-PET/CT Dosimetric Comparison of rhTSH versus Thyroid Hormone Withholding Before Radioiodine Remnant Ablation in Differentiated Thyroid Cancer

Abstract

Aim: Recombinant human thyroid-stimulating hormone (rhTSH) recently was approved as an alternative to thyroid hormone withholding (THW) to elevate TSH for thyroid remnant ablation in differentiated thyroid carcinoma patients. High ablation success rates are reported with diverse rhTSH-aided ¹³¹I activities. Improved renal function causes ∼50% faster radioiodine clearance under euthyroidism versus hypothyroidism. Knowledge of comparative remnant radioiodine kinetics, particularly the remnant radiation dose in Gy/GBq of administered ¹³¹I activity (RDpA), could assist in choosing rhTSH-aided ablative activities.

Material and Methods: To compare the RDpA, determined through ¹²⁴I-positron emission tomography/computed tomography (PET/CT), under the two stimulation methods, we retrospectively divided into two groups 55 consecutive totally-thyroidectomized, radioiodine-naïve patients. The rhTSH group (n=16) received ¹²⁴I on thyroid hormone, 24 h after two consecutive daily intramuscular injections of rhTSH, 0.9 mg. The THW group (n=39) received ¹²⁴I after weeks-long THW, when serum TSH first measured ≥25 mIU/L. We performed PET investigations 4 h, 24 h, 48 h, 72 h and 96 h and PET/CT 25 h after ¹²⁴I administration.

Results: Median stimulated serum thyroglobulin was 15 times higher (p=0.023) and M1 disease almost twice as prevalent (p=0.05) in rhTSH versus THW patients. Mean±standard deviation RDpA was statistically equivalent between the groups: rhTSH, 461±600 Gy/GBq, THW, 302±329 Gy/GBq, two-sided p=0.258.

Conclusions: rhTSH or THW deliver statistically equivalent radiation doses to thyroid remnant and may be chosen based on safety, quality-of-life, convenience and pharmacoeconomic factors. Institutional fixed radioiodine activities formulated for use with THW need not be adjusted for rhTSH-aided ablation.

Key words

differentiated thyroid carcinoma - thyroid remnant - thyroid remnant dose - thyroid remnant ablation - 124-iodine - 131-iodine - radioiodine - positron emission tomography - computed tomography - dosimetry - recombinant human thyroid-stimulating hormone - thyroid hormone withholding - remnant dose per administered activity

References

• 1 Andermann P, Schlogl S, Mader U. et al . Intra- and interobserver variability of thyroid volume measurements in healthy adults by 2D versus 3D ultrasound.  Nuklearmedizin. 2007;  46 1-7
• 2 Barbaro D, Boni G, Meucci G. et al . Recombinant human thyroid-stimulating hormone is effective for radioiodine ablation of post-surgical thyroid remnants.  Nucl Med Commun. 2006;  27 627-632
• 3 Chianelli M, Todino V, Graziano F. et al . Low dose (2.0 GBq; 54 mCi) radioiodine postsurgical remnant ablation in thyroid cancer: comparison between hormone withdrawal and use of rhTSH in low risk patients.  Eur J Endocrinol. 2008;  e-publication 
• 4 Eschmann SM, Reischl G, Bilger K. et al . Evaluation of dosimetry of radioiodine therapy in benign and malignant thyroid disorders by means of iodine-124 and PET.  Eur J Nucl Med Mol Imaging. 2002;  29 760-767
• 5 Fleming ID CJ, Henson DE. (eds) AJCC Cancer Staging Manual, 5^th ed. Lippincott-Raven, Philadelphia, PA 1997
• 6 Freudenberg L, Bockisch A, Jentzen W. ¹²⁴I positron emission tomographic dosimetry and position emission tomography/computed tomography imaging in differentiated thyroid cancer. In: H Biersack, F Grunwald.(eds) Thyroid Cancer, 2^nd ed. Springer, Berlin 2005
• 7 Freudenberg L, Jentzen W, Goerges R. et al . ¹²⁴I-PET dosimetry in advanced differentiated thyroid cancer.  Therapeutic impact. Nuklearmedizin. 2007a;  46 121-128
• 8 Freudenberg LS, Jentzen W, Marlowe RJ. et al . 124-iodine positron emission tomography/computed tomography dosimetry in pediatric patients with differentiated thyroid cancer.  Exp Clin Endocrinol Diabetes. 2007b;  115 690-693
• 9 Furhang EE, Larson SM, Buranapong P. et al . Thyroid cancer dosimetry using clearance fitting.  J Nucl Med. 1999;  40 131-136
• 10 Gorges R, Eising EG, Fotescu D. et al . Diagnostic value of high-resolution B-mode and power-mode sonography in the follow-up of thyroid cancer.  Eur J Ultrasound. 2003;  16 191-206
• 11 Hackshaw A, Harmer C, Mallick U. et al . ¹³¹I activity for remnant ablation in patients with differentiated thyroid cancer: A systematic review.  J Clin Endocrinol Metab. 2007;  92 28-38
• 12 Hanscheid H, Lassmann M, Luster M. et al . 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.  J Nucl Med. 2006;  47 648-654
• 13 Haugen BR, Pacini F, Reiners C. et al . A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer.  J Clin Endocrinol Metab. 1999;  84 3877-3885
• 14 Jentzen W, Freudenberg L, Eising EG. et al . Segmentation of PET volumes by iterative image thresholding.  J Nucl Med. 2007;  48 108-114
• 15 Jentzen W, Freudenberg L, Eising EG. et al . Optimized ¹²⁴I PET dosimetry protocol for radioiodine therapy of differentiated thyroid cancer.  J Nucl Med. 2008a;  49 1017-1023
• 16 Jentzen W, Weise R, Kupferschlager J. et al . Iodine-¹²⁴ PET dosimetry in differentiated thyroid cancer: recovery coefficient in 2D and 3D modes for PET(/CT) systems.  Eur J Nucl Med Mol Imaging. 2008b;  35 611-623
• 17 Knust EJ, Dutschka K, Weinreich R. Preparation of ¹²⁴I solutions after thermodistillation of irradiated 124TeO2 targets.  Appl Radiat Isot. 2000;  52 181-184
• 18 Ladenson PW, Braverman LE, Mazzaferri EL. et al . Comparison of administration of recombinant human thyrotropin with withdrawal of thyroid hormone for radioactive iodine scanning in patients with thyroid carcinoma.  N Engl J Med. 1997;  337 888-896
• 19 Lassmann M, Luster M, Hanscheid H. et al . Impact of ¹³¹I diagnostic activities on the biokinetics of thyroid remnants.  J Nucl Med. 2004;  45 619-625
• 20 Loevinger R, Budinger TF, Watson EE. MIRD primer for absorbed dose calculations. Society of Nuclear Medicine, New York 1991
• 21 Luster M, Felbinger R, Dietlein M. et al . Thyroid hormone withdrawal in patients with differentiated thyroid carcinoma: a one hundred thirty-patient pilot survey on consequences of hypothyroidism and a pharmacoeconomic comparison to recombinant thyrotropin administration.  Thyroid. 2005;  15 1147-1155
• 22 Luster M, Sherman SI, Skarulis MC. et al . Comparison of radioiodine biokinetics following the administration of recombinant human thyroid stimulating hormone and after thyroid hormone withdrawal in thyroid carcinoma.  Eur J Nucl Med Mol Imaging. 2003;  30 1371-1377
• 23 Maxon 3rd  HR, Englaro EE, Thomas SR. et al . Radioiodine-131 therapy for well-differentiated thyroid cancer – a quantitative radiation dosimetric approach: outcome and validation in 85 patients.  J Nucl Med. 1992;  33 1132-1136
• 24 Pacini F, Molinaro E, Castagna MG. Ablation of thyroid residues with 30 mCi (131)I: a comparison in thyroid cancer patients prepared with recombinant human TSH or thyroid hormone withdrawal.  J Clin Endocrinol Metab. 2002;  87 4063-4068
• 25 Pacini F, Ladenson PW, Schlumberger M. et al . Radioiodine ablation of thyroid remnants after preparation with recombinant human thyrotropin in differentiated thyroid carcinoma: results of an international, randomized, controlled study.  J Clin Endocrinol Metab. 2006;  91 926-932
• 26 Park S-G, Reynolds JC, Brucker-Davis F. et al . Iodine kinetics during I-131 scanning in patients with thyroid cancer: comparison of studies with recombinant human TSH (rhTSH) vs. hypothyroidism [abstract].  J Nucl Med. 1996;  37 15P, abstr 49 
• 27 Pilli T, Brianzoni E, Capoccetti F. et al . A comparison of 1 850 (50 mCi) and 3 700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.  J Clin Endocrinol Metab. 2007;  92 3542-3546
• 28 Remy H, Borget I, Leboulleux S. et al . ¹³¹I Effective Half-Life and Dosimetry in Thyroid Cancer Patients.  J Nucl Med. 2008;  49 1445-1450
• 29 Robbins RJ, Larson SM, Sinha N. et al . A retrospective review of the effectiveness of recombinant human TSH as a preparation for radioiodine thyroid remnant ablation.  J Nucl Med. 2002;  43 1482-1488
• 30 Rosario PW, Borges MA, Purisch S. Preparation with recombinant human thyroid-stimulating hormone for thyroid remnant ablation with ¹³¹I is associated with lowered radiotoxicity.  J Nucl Med. 2008;  49 1776-1782
• 31 Schlumberger MJ. Papillary and follicular thyroid carcinoma.  N Engl J Med. 1998;  338 297-306
• 32 Schroeder PR, Haugen BR, Pacini F. et al . A comparison of short-term changes in health-related quality of life in thyroid carcinoma patients undergoing diagnostic evaluation with recombinant human thyrotropin compared with thyroid hormone withdrawal.  J Clin Endocrinol Metab. 2006;  91 878-884
• 33 Snyder W, Ford MR, Warner GG. et al .“S”, Absorbed dose per unit cumulated activity for selected radionuclides and organs. Society of Nuclear Medicine, New York, NY 1975
• 34 Taieb D, Sebag F, Cherenko M. et al .Quality of life changes and clinical outcomes in thyroid cancer patients undergoing radioiodine remnant ablation with recombinant human thyrotropin: a randomized controlled study. Clin Endocrinol (Oxf). 2008 e-publication
• 35 Tuttle RM, Brokhin M, Omry G. et al . Recombinant human TSH-assisted radioactive iodine remnant ablation achieves short-term clinical recurrence rates similar to those of traditional thyroid hormone withdrawal.  J Nucl Med. 2008;  49 764-770
• 36 Vaiano A, Claudio Traino A, Boni G. et al . Comparison between remnant and red-marrow absorbed dose in thyroid cancer patients submitted to ¹³¹I ablative therapy after rh-TSH stimulation versus hypothyroidism induced by L-thyroxine withdrawal.  Nucl Med Commun. 2007;  28 215-223
• 37 Weinreich R, Knust EJ. Quality assurance of iodine-124 produced via the nuclear reaction 124Te(d, 2n)¹²⁴I.  J Radioanal Nucl Chem Lett. 1996;  213 253-261

Correspondence