Abstract
Aim
Differentiated thyroid cancer is characterized by a very good prognosis in the majority of the patients. The therapy of choice is surgery followed by ablation with Iodine-131 (I-131). However, some patients have metastases that have lost the capability of concentrating I-131, even when it is given in therapeutic doses. In the present study, we describe the value of Indium-111 Octreotide (Octreoscan) in differentiated thyroid cancer patients with increased Tg levels who failed to demonstrate a response to treatment with high-dose I-131.
Method
Fifteen consecutive patients with progressive differentiated thyroid cancer (ten female, five male) (mean age: 59 years, range 13–81 years; eight papillary, six follicular, and one Hürthle cell carcinoma) were studied. Progression was based on increasing Tg levels and was confirmed by radiological evaluation. Whole body scintigraphy (WBS) was performed after the administration of 200 MBq of Indium-111-Octreotide. The images were assessed by two experienced observers and compared with post-treatment I-131 WBS.
Results
In seven out of 15 patients distant metastases were already present at initial stage, whereas in ten patients the primary tumor stage was T3 or T4 indicating that the majority of the patients had advanced disease. In two out of five patients with a positive I-131 WBS, Indium-111-Octreotide was false negative. In nine out of ten patients with a negative I-131 WBS, Indium-111-Octreotide demonstrated multiple metastases. In those patients with a positive SSR-scintigraphy, metastases were found in the lungs (n=14), bone (n=7), mediastinum (n=3), liver (n=2), brains (n=1), and cutis (n=1). Overall, three out of 15 patients had a negative Indium-111-Octreotide result revealing a sensitivity of 80%.
Conclusion
Our findings demonstrate the diagnostic value of Indium-111-Octreotide in differentiated thyroid cancer that fails to respond to I-131 treatment. It opens the possibility for additional treatment with high doses of Indium-111-Octreotide or its analogs in a majority of the patients.
Similar content being viewed by others
References
Ain KB, Taylor KD, Tofiq S, Venkataraman G (1997) Somatostatin receptor subtype expression in human thyroid and thyroid carcinoma cell lines. J Clin Endocrinol Metab 82:1857–1862
Baudin E, Schlumberger M, Lumbroso J, Travagli JP, Caillou B, Parmentier C (1996) Octreotide scintigraphy in patients with differentiated thyroid carcinoma: contribution for patients with negative radioiodine scan. J Clin Endocrinol Metab 81:2541–2544
Bernier MO, Leenhardt L, Hoang C, Aurengo A, Mary JY, Menegaux F, Enkaoua E, Turpin G, Chiras J, Saillant G, Hejblum G (2001) Survival and therapeutic modalities in patients with bone metastases of differentiated thyroid carcinomas. J Clin Endocrinol Metab 86:1568–1573
Brendel AJ, Guyot M, Jeandot R, Lefort G, Manciet G (1988) Thallium-201 imaging in the follow-up of differentiated thyroid carcinoma. J Nucl Med 29:1515–1520
Casara D, Rubello D, Saladini G, Masarotto G, Favero A, Girelli ME, Busnardo B (1993) Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables. J Nucl Med 34:1626–1631
de Jong M, Breeman WA, Bernard BF, Bakker WH, Visser TJ, Kooij PP, van Gameren A, Krenning EP (2001) Tumor response after [(90)Y-DOTA(0),Tyr(3)]octreotide radionuclide therapy in a transplantable rat tumor model is dependent on tumor size. J Nucl Med 42:1841–1846
de Jong M, Valkema R, Jamar F, Kvols LK, Kwekkeboom DJ, Breeman WA, Bakker WH, Smith C, Pauwels S, Krenning EP (2002) Somatostatin receptor-targeted radionuclide therapy of tumors: preclinical and clinical findings. Semin Nucl Med 32:133–140
Dietlein M, Scheidhauer K, Voth E, Theissen P, Schicha H (1998) Follow-up of differentiated thyroid cancer: what is the value of FDG and sestamibi in the diagnostic algorithm? Nuklearmedizin 37:12–17
Feine U, Lietzenmayer R, Hanke JP, Held J, Wohrle H, Muller-Schauenburg W (1996) Fluorine-18-FDG and iodine-131-iodide uptake in thyroid cancer. J Nucl Med 37:1468–1472
Forssell-Aronsson EB, Nilsson O, Bejegard SA, Kolby L, Bernhardt P, Molne J, Hashemi SH, Wangberg B, Tisell LE, Ahlman H (2000) 111In-DTPA-D-Phe1-octreotide binding and somatostatin receptor subtypes in thyroid tumors. J Nucl Med 41:636–642
Garin E, Devillers A, Le Cloirec J, Bernard AM, Lescouarc'h J, Herry JY, Reubi JC, Bourguet P (1998) Use of indium-111 pentetreotide somatostatin receptor scintigraphy to detect recurrent thyroid carcinoma in patients without detectable iodine uptake. Eur J Nucl Med 25:687–694
Görges R, Kahaly G, Muller-Brand J, Macke H, Roser HW, Bockisch A (2001) Radionuclide-labeled somatostatin analogues for diagnostic and therapeutic purposes in nonmedullary thyroid cancer. Thyroid 11:647–659
Grunwald F, Schomburg A, Bender H, Klemm E, Menzel C, Bultmann T, Palmedo H, Ruhlmann J, Kozak B, Biersack HJ (1996) Fluorine-18 fluorodeoxyglucose positron emission tomography in the follow-up of differentiated thyroid cancer. Eur J Nucl Med 23:312–319
Haslinghuis LM, Krenning EP, de Herder WW, Reijs AE, Kwekkeboom DJ (2001) Somatostatin receptor scintigraphy in the follow-up of patients with differentiated thyroid cancer. J Endocrinol Invest 24:415–422
Haugen BR (1999) Management of the patient with progressive radioiodine non-responsive disease. Semin Surg Oncol 16:34–41
Hoelting T, Duh QY, Clark OH, Herfarth C (1996) Somatostatin analog octreotide inhibits the growth of differentiated thyroid cancer cells in vitro, but not in vivo. J Clin Endocrinol Metab 81:2638–2641
Krenning EP, Kooij PP, Pauwels S, Breeman WA, Postema PT, de Herder WW, Valkema R, Kwekkeboom DJ (1996) Somatostatin receptor: scintigraphy and radionuclide therapy. Digestion 57[Suppl 1]:57–61
Krenning EP, de Jong M, Kooij PP, Breeman WA, Bakker WH, de Herder WW, van Eijck CH, Kwekkeboom DJ, Jamar F, Pauwels S, Valkema R (1999) Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol 10[Suppl 2]: S23-S29
Lazar V, Bidart JM, Caillou B, Mahe C, Lacroix L, Filetti S, Schlumberger M (1999) Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. J Clin Endocrinol Metab 84:3228–3234
Lin JD, Kao PF, Weng HF, Lu WT, Huang MJ (1998) Relative value of thallium-201 and iodine-131 scans in the detection of recurrence or distant metastasis of well differentiated thyroid carcinoma. Eur J Nucl Med 25:695–700
Lorberboym M, Murthy S, Mechanick JI, Bergman D, Morris JC, Kim CK (1996) Thallium-201 and iodine-131 scintigraphy in differentiated thyroid carcinoma. J Nucl Med 37:1487–1491
Maxon HR (1999) Quantitative radioiodine therapy in the treatment of differentiated thyroid cancer. Q J Nucl Med 43:313–323
McCarthy KE, Woltering EA, Anthony LB (2000) In situ radiotherapy with 111In-pentetreotide. State of the art and perspectives. Q J Nucl Med 44:88–95
Miyamoto S, Kasagi K, Misaki T, Alam MS, Konishi J (1997) Evaluation of technetium-99m-MIBI scintigraphy in metastatic differentiated thyroid carcinoma. J Nucl Med 38:352–356
Nakada K, Katoh C, Kanegae K, Tsukamoto E, Shiga T, Mochizuki T, Itoh K, Tamaki N (1998) Thallium-201 scintigraphy to predict therapeutic outcome of iodine-131 therapy of metastatic thyroid carcinoma. J Nucl Med 39:807–810
Nemec J, Nyvltova O, Blazek T, Vlcek P, Racek P, Novak Z, Preiningerova M, Hubackova M, Krizo M, Zimak J, Bilek R (1996) Positive thyroid cancer scintigraphy using technetium-99m methoxyisobutylisonitrile. Eur J Nucl Med 23:69–71
Pachucki J, Burmeister LA (1997) Evaluation and treatment of persistent thyroglobulinemia in patients with well-differentiated thyroid cancer. Eur J Endocrinol 137:254–261
Pauwels EK, Ribeiro MJ, Stoot JH, McCready VR, Bourguignon M, Maziere B (1998) FDG accumulation and tumor biology. Nucl Med Biol 25:317–322
Postema PT, de Herder WW, Reubi JC, Oei HY, Kwekkeboom DJ, Bruining HJ, Bonjer J, van Toor H, Hennemann G, Krenning EP (1996) Somatostatin receptor scintigraphy in non-medullary thyroid cancer. Digestion 57[Suppl 1]:36–37
Reubi JC, Schar JC, Waser B, Wenger S, Heppeler A, Schmitt JS, Macke HR (2000) Affinity profiles for human somatostatin receptor subtypes SST1-SST5 of somatostatin radiotracers selected for scintigraphic and radiotherapeutic use. Eur J Nucl Med 27:273–282
Reubi JC, Waser B, Schaer JC, Laissue JA (2001) Somatostatin receptor sst1-sst5 expression in normal and neoplastic human tissues using receptor autoradiography with subtype-selective ligands. Eur J Nucl Med 28:836–846
Robbins RJ, Hill RH, Wang W, Macapinlac HH, Larson SM (2000) Inhibition of metabolic activity in papillary thyroid carcinoma by a somatostatin analogue. Thyroid 10:177–183
Roelants V, Nayer PD, Bouckaert A, Beckers C (1997) The predictive value of serum thyroglobulin in the follow-up of differentiated thyroid cancer. Eur J Nucl Med 24:722–727
Rubello D, Saladini G, Carpi A, Casara D (2000a) Nuclear medicine imaging procedures in differentiated thyroid carcinoma patients with negative iodine scan. Biomed Pharmacother 54:337–344
Rubello D, Mazzarotto R, Casara D (2000b) The role of technetium-99m methoxyisobutylisonitrile scintigraphy in the planning of therapy and follow-up of patients with differentiated thyroid carcinoma after surgery. Eur J Nucl Med 27:431–440
Rubello D, Piotto A, Pagetta C, Pelizzo MR, Casara D (2002) (99m)Tc-MIBI radio-guided surgery for recurrent thyroid carcinoma: technical feasibility and procedure, and preliminary clinical results. Eur J Nucl Med Mol Imaging 29:1201–1205
Schlumberger MJ (1998) Papillary and follicular thyroid carcinoma. N Engl J Med 338:297–306
Schlumberger M, Baudin E (1998) Serum thyroglobulin determination in the follow-up of patients with differentiated thyroid carcinoma. Eur J Endocrinol 138:249–252
Smith-Jones PM, Bischof C, Leimer M, Gludovacz D, Angelberger P, Pangerl T, Peck-Radosavljevic M, Hamilton G, Kaserer K, Kofler A, Schlangbauer-Wadl H, Traub T, Virgolini I (1999) DOTA-lanreotide: a novel somatostatin analog for tumor diagnosis and therapy. Endocrinology 140:5136–5148
Stokkel MP, de Klerk JH, Zelissen PM, Koppeschaar HP, van Rijk PP (1999) Fluorine-18 fluorodeoxyglucose dual-head positron emission tomography in the detection of recurrent differentiated thyroid cancer: preliminary results. Eur J Nucl Med 26:1606–1609
Sundram FX, Goh AS, Ang ES (1993) Role of technetium-99m sestamibi in localisation of thyroid cancer metastases. Ann Acad Med Singapore 22:557–559
Uematsu H, Sadato N, Ohtsubo T, Tsuchida T, Nakamura S, Sugimoto K, Waki A, Takahashi N, Yonekura Y, Tsuda G, Saito H, Hayashi N, Yamamoto K, Ishii Y (1998) Fluorine-18-fluorodeoxyglucose PET versus thallium-201 scintigraphy evaluation of thyroid tumors. J Nucl Med 39:453–459
van den Brekel MW (2000) Lymph node metastases: CT and MRI. Eur J Radiol 33:230–238
van den Brekel MW, Castelijns JA (2000) Imaging of lymph nodes in the neck. Semin Roentgenol 35:42–53
Van Wyngaarden KE, Pauwels EK (1995) Fluorodeoxyglucose (FDG) and tumor metabolism. Nucl Med Commun 16:987–989
Vassilopoulou-Sellin R (2001) Long-term outcome of children with papillary thyroid cancer. Surgery 129:769
Vassilopoulou-Sellin R, Schultz PN, Haynie TP (1996) Clinical outcome of patients with papillary thyroid carcinoma who have recurrence after initial radioactive iodine therapy. Cancer 78:493–501
Virgolini I, Traub T, Novotny C, Leimer M, Fuger B, Li SR, Patri P, Pangerl T, Angelberger P, Raderer M, Andreae F, Kurtaran A, Dudczak R (2001) New trends in peptide receptor radioligands. Q J Nucl Med 45:153–159
Virgolini I, Traub T, Novotny C, Leimer M, Fuger B, Li SR, Patri P, Pangerl T, Angelberger P, Raderer M, Burggasser G, Andreae F, Kurtaran A, Dudczak R (2002) Experience with indium-111 and yttrium-90-labeled somatostatin analogs. Curr Pharm Des 8:1781–1807
Wang W, Larson SM, Fazzari M, Tickoo SK, Kolbert K, Sgouros G, Yeung H, Macapinlac H, Rosai J, Robbins RJ (2000) Prognostic value of [18F]fluorodeoxyglucose positron emission tomographic scanning in patients with thyroid cancer. J Clin Endocrinol Metab 85:1107–1113
Weckbecker G, Liu R, Tolcsvai L, Bruns C (1992) Antiproliferative effects of the somatostatin analogue octreotide (SMS 201–995) on ZR-75–1 human breast cancer cells in vivo and in vitro. Cancer Res 52:4973–4978
Weckbecker G, Raulf F, Tolcsvai L, Bruns C (1996) Potentiation of the anti-proliferative effects of anti-cancer drugs by octreotide in vitro and in vivo. Digestion 57[Suppl 1]:22–28
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stokkel, M.P.M., Reigman, H.I.E., Verkooijen, R.B.T. et al. Indium-111-Octreotide scintigraphy in differentiated thyroid carcinoma metastases that do not respond to treatment with high-dose I-131. J Cancer Res Clin Oncol 129, 287–294 (2003). https://doi.org/10.1007/s00432-003-0435-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-003-0435-9