Abstract
Purpose
Radioiodine-negative thyroid cancer presents diagnostic and therapeutic difficulties, warranting the implementation of new imaging and treatment strategies. The purpose of this study was twofold. First, we investigated in vitro the binding characteristics of 111In-DOTA-lanreotide (111In-DOTA-LAN) and 111In-DOTA-DPhe1-Tyr3-octreotide (111In-DOTA-TOC) to cells derived from differentiated thyroid cancer (DTC). Second, we evaluated the value of somatostatin receptor (SSTR) scintigraphy with these radioligands, as compared with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), for the detection of tumour lesions in DTC patients.
Methods
Binding of 111In-DOTA-LAN and 111In-DOTA-TOC to cells isolated from surgically removed thyroid tissue was evaluated in vitro by performing saturation and displacement studies. Eighteen DTC patients with elevated thyroglobulin (12 radioiodine-negative, six radioiodine-positive) were investigated with 111In-DOTA-LAN, 111In-DOTA-TOC and 18F-FDG PET scans.
Results
Large numbers of SSTR binding sites for 111In-DOTA-LAN and 111In-DOTA-TOC were found on the cells investigated. Both SSTR radioligands exhibited a high binding affinity for these SSTR binding sites. 111In-DOTA-LAN and 111In-DOTA-TOC scintigraphy detected 37 and 33 lesions, respectively, in 17 (94%) patients each, whereas 18F-FDG PET revealed 30 lesions in 15 (83%) patients. Uptake of both SSTR radioligands was found in several radioiodine-negative sites. No striking differences in lesion imaging by 111In-DOTA-LAN and 111In-DOTA-TOC were found. In both radioiodine-negative and radioiodine-positive patients, more lesions were SSTR-positive/18F-FDG-negative than were 18F-FDG-positive/SSTR-negative.
Conclusion
Adding a SSTR scan with these radioligands to the diagnostic work-up increases the diagnostic capacity in DTC, and should be considered particularly in radioiodine-negative patients with elevated thyroglobulin levels.
Similar content being viewed by others
References
Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A national cancer data base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985–1995. Cancer 1998;83:2638–48.
Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994;97:418–28.
Singer PA, Cooper DS, Daniels GH, Ladenson PW, Greenspan FS, Levi EG, et al. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. Arch Intern Med 1996;156:2165–72.
Ronga G, Fiorentino A, Paserio E, Signore A, Todino V, Tummarello MA, et al. Can iodine-131 whole body scan be replaced by thyroglobulin measurement in the post-surgical follow-up of differentiated thyroid carcinoma? J Nucl Med 1990;31:1766–71.
Arning G, Ehrenheim C, Schober O, Hundeshagen H. 131I-accumulating pulmonary and bone metastases of differentiated thyroid cancer with low serum thyroglobulin levels—an exception in tumor follow-up? Nuklearmediziner 1987;26:139–42.
McDougall IR. 131I treatment of 131I negative whole body scan, and positive thyroglobulin in differentiated thyroid carcinoma: what is being treated? Thyroid 1997;7:669–72.
Samaan NA, Schultz PN, Haynie TP, Ordonez NG. Pulmonary metastasis of differentiated thyroid carcinoma: treatment results in 101 patients. J Clin Endocrinol Metab 1995;60:376–80.
Frilling A, Tecklenborg K, Gorges R, Weber F, Clausen M, Broelsch EC. Preoperative diagnostic value of [18F] fluorodeoxyglucose positron emission tomography in patients with radioiodine-negative recurrent well-differentiated thyroid carcinoma. Ann Surg 2001;234:804–11.
Lind P, Kresnik E, Kumnig G, Gallowitsch HJ, Igerc I, Matschnig S, et al. 18F-FDG-PET in the follow-up of thyroid cancer. Acta Med Austriaca 2003;30:17–21.
Grunwald F, Kalicke T, Feine U, Lietzenmayer R, Scheidhauer K, Dietlein M, et al. Fluorine-18 fluorodeoxyglucose positron emission tomography in thyroid cancer: results of a multicentre study. Eur J Nucl Med 1999;26:1547–52.
Nishiyama Y, Yamamoto Y, Ono Y, Takahashi K, Nakano S, Satoh K, et al. Comparison of 99Tcm-tetrofosmin with 201Tl and 131I in the detection of differentiated thyroid cancer metastases. Nucl Med Commun 2000;21:917–23.
Gallowitsch HJ, Mikosch P, Kresnik E, Unterweger O, Gomez I, Lind P. Thyroglobulin and low-dose iodine-131 and technetium-99m-tetrofosmin whole-body scintigraphy in differentiated thyroid carcinoma. J Nucl Med 1998;39:870–5.
Chen YK, Liu FY, Yen RF, Kao CH. Compare FDG-PET and Tc-99m tetrofosmin SPECT to detect metastatic thyroid carcinoma. Acad Radiol 2003;10:835–9.
Virgolini I, Yang Q, Li S, Angelberger P, Neuhold N, Niederle B, et al. Cross-competition between vasoactive intestinal peptide and somatostatin for binding to tumor cell membrane receptors. Cancer Res 1994;54:690–700.
Cremonesi M, Ferrari M, Zoboli S, Chinol M, Stabin MG, Orsi F, et al. Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC. Eur J Nucl Med 1999;26:877–86.
Kölby L, Wängberg B, Ahlman H, Tisell LE, Fjälling M, Forssell-Aronsson E, et al. Somatostatin receptor subtypes, octreotide scintigraphy, and clinical response to octreotide treatment in patients with neuroendocrine tumors. World J Surg 1998;22:679–83.
Krenning EP, Kwekkeboom DJ, Bakker WH, Breeman WA, Kooij PP, Oei HY, et al. Somatostatin receptor scintigraphy with [111In-DTPA-d-Phe1]- and [123I-Tyr3]-octreotide: the Rotterdam experience with more than 1000 patients. Eur J Nucl Med 1993;20:716–31.
Virgolini I, Angelberger P, Li S, Yang Q, Kurtaran A, Raderer M, et al. In vitro and in vivo studies of three radiolabelled somatostatin analogues: 123I-octreotide, 123I-Tyr-3-octreotide and 111In-DTPA-Phe-1-octreotide. Eur J Nucl Med 1996;23:1388–99.
Virgolini I, Britton K, Buscombe J, Moncayo R, Paganelli G, Riva P. 111In- and 90Y-DOTA-lanreotide: results and implications of the MAURITIUS trial. Semin Nucl Med 2002;32:148–55.
Virgolini I, Patri P, Novotny C, Traub T, Leimer M, Füger B, et al. Comparative somatostatin receptor scintigraphy using In-111-DOTA-lanreotide and In-111-DOTA-Tyr3-octreotide versus F-18-FDG-PET for evaluation of somatostatin receptor-mediated radionuclide therapy. Ann Oncol 2001;12 Suppl. 2:41–5.
Ain KB, Taylor KD, Tofiq S, Venkataraman G. Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines. J Clin Endocrinol Metab 1997;82:1857–62.
Baudin E, Schlumberger M, Lumbroso J, Travagli JP, Caillou B, Parmentier C. Octreotide scintigraphy in patients with differentiated thyroid carcinoma: contribution for patients with negative radioiodine scan. J Clin Endocrinol Metab 1996;81:2541–4.
Sarlis NJ, Gourgiotis L, Guthrie LC, Galen B, Skarulis MC, Shawker TH, et al. In-111 DTPA-octreotide scintigraphy for disease detection in metastatic thyroid cancer: comparison with F-18 FDG positron emission tomography and extensive conventional radiographic imaging. Clin Nucl Med 2003;28:208–17.
Gorges R, Kahaly G, Muller-Brand J, Macke H, Roser HW, Bockisch A. Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer. Thyroid 2001;11:647–59.
Krenning EP, Kooij PP, Bakker WH, Breeman WA, Postema PT, Kwekkeboom DJ, et al. Radiotherapy with a radiolabeled somatostatin analogue, [111In-DTPA-d-Phe1]-octreotide. A case history. Ann N Y Acad Sci 1994;733:496–506.
Bernhardt P, Forssell-Aronsson E, Jacobsson L, Skarnemark G. Low-energy electron emitters for targeted therapy of small tumors. Acta Oncol 2001;41:602–8.
Otte A, Jermann E, Behe M, Goetze M, Bucher HC, Roser HW, et al. DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy. Eur J Nucl Med 1997;24:792–5.
Smith-Jones P, Bischof C, Leimer M, Gludovacz D, Angelberger P, Pangerl T, et al. DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy. Endocrinology 1999;140:5136–48.
Reubi JC, Schaer JC, Waser B, Wenger S, Heppeler A, Schmitt JS, et al. Affinity profiles for human somatostatin receptor subtypes SST1–SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 2000;27:273–82.
Wu YT, Hsieh HP, Wu CY, Yu HM, Chen ST, Wang KT. Facile solid phase synthesis of octreotide analogs using p-carboxybenzaldehyde as a novel linker for anchor Fmoc-threoninol to the solid phase resin. Tetrahedron Lett 1998;39:1783–4.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248–54.
Scatchard G. The attraction of proteins for small molecules and ions. Ann N Y Acad Sci 1949;51:660–72.
Loevinger R, Budinger TF, Watson EE. MIRD primer for absorbed dose calculations. The Society of Nuclear Medicine, New York; 1998.
Virgolini I, Szilvasi I, Kurtaran A, Angelberger P, Raderer M, Havlik E, et al. Indium-111-DOTA-lanreotide: biodistribution, safety and radiation absorbed dose in tumor patients. J Nucl Med 1998;39:1928–36.
Garin E, Devillers A, Le Cloirec J, Bernard AM, Lescouarc’h J, Herry JY, et al. Use of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients without detectable iodine uptake. Eur J Nucl Med 1998;25:687–94.
Khan N, Oriuchi N, Higuchi T, Zhang H, Endo K. PET in the follow-up of differentiated thyroid cancer. Br J Radiol 2003;76:690–5.
Feine U, Leitzenmayer R, Hanke JP, Held J, Wohrle H, Muller-Schauenburg W. Fluorine-18-FDG and iodine-131-iodide uptake in thyroid cancer. J Nucl Med 1996;37:1468–72.
Giammarile F, Hafdi Z, Bournaud C, Janier M, Houzard C, Desuzinges C, et al. Is [18F]-2-fluoro-2-deoxy-d-glucose (FDG) scintigraphy with non-dedicated positron emission tomography useful in the diagnostic management of suspected metastatic thyroid carcinoma in patients with no detectable radioiodine uptake? Eur J Endocrinol 2003;149:293–300.
Paganelli G, Zoboli S, Cremonesi M, Bodei L, Ferrari M, Grana C, et al. Receptor-mediated radiotherapy with 90Y-DOTA-d-Phe1-Tyr3-octreotide. Eur J Nucl Med Mol Imaging 2001;28:426–34.
Acknowledgements
We thank our staff members Thomas Pangerl, Kurt Kaserer and Phillip Patri for their excellent cooperation during the performance of the study, and all technologists involved in the acquisition and processing of the scintigraphic data. The clinical collaboration of Drs. Juan Flores, Clemens Novotny, Michaela Greifeneder, Silvia Wogritsch, Ingrid Hurtl, Amir Kurtaran and Kurt Kletter is highlighted. We are grateful to Emilia Halvadjieva, Ernst Havlik, Bettina Ibi and Ruth Freund for their persistent help in our dosimetric calculations. These studies were supported in part by the Austrian National Bank (Anniversary Foundation, Projects No. 7487 and 8185) and by a Foundation of the Mayor of the City of Vienna.
Author information
Authors and Affiliations
Corresponding author
Additional information
These studies were supported in part by the Austrian National Bank (Anniversary Foundation, Projects No. 7487 and 8185) and by a Foundation of the Mayor of the City of Vienna.
Rights and permissions
About this article
Cite this article
Rodrigues, M., Traub-Weidinger, T., Leimer, M. et al. Value of 111In-DOTA-lanreotide and 111In-DOTA-DPhe1-Tyr3-octreotide in differentiated thyroid cancer: results of in vitro binding studies and in vivo comparison with 18F-FDG PET. Eur J Nucl Med Mol Imaging 32, 1144–1151 (2005). https://doi.org/10.1007/s00259-005-1820-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-005-1820-1