Abstract
To evaluate the use of pretargeted immunoscintigraphy (ISG) in the diagnosis and follow-up of patients with medullary thyroid carcinoma (MTC), we studied 25 patients with histologically proven disease; ISG was repeated after surgery in two patients. The antibody, either an anticarcinoembryonic antigen (CEA) or an antichromogranin A (CgA) biotinylated monoclonal antibody (MAb) or a cocktail of the two biotinylated MAbs was first injected. After 24 h, avidin was administrated i.v., followed by 111In-labelled biotin 24 h later. Fifty-two lesions were visualised. Six primary tumours, diagnosed by increased calcitonin levels, were all correctly diagnosed; 47 recurrences, also suspected by blood tumour markers, were detected and confirmed by cytology or histology. In one case, single photon emission tomography allowed the detection of small lymph nodes with a diameter of 4-7 mm. These lesions, not judged neoplastic by ultrasound, were confirmed to be neoplastic by fine needle aspiration. Pretargeted ISG correctly localises primary tumours and recurrences in MTC patients, when the only marker of relapse is serum elevation of calcitonin. With this three-step pretargeting method, cocktails of potentially useful MAbs can be used, avoiding false-negative studies that may occur when CEA or CgA are not expressed.
Full text
PDF






Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adams B. K., Fataar A., Byrne M. J., Levitt N. S., Matley P. J. Pentavalent technetium-99m (V)-DMSA uptake in a pheochromocytoma in a patient with Sipple's syndrome. J Nucl Med. 1990 Jan;31(1):106–108. [PubMed] [Google Scholar]
- Arnstein N. B., Juni J. E., Sisson J. C., Lloyd R. V., Thompson N. W. Recurrent medullary carcinoma of the thyroid demonstrated by thallium-201 scintigraphy. J Nucl Med. 1986 Oct;27(10):1564–1568. [PubMed] [Google Scholar]
- Baulieu J. L., Guilloteau D., Delisle M. J., Perdrisot R., Gardet P., Delépine N., Baulieu F., Dupont J. L., Talbot J. N., Coutris G. Radioiodinated meta-iodobenzylguanidine uptake in medullary thyroid cancer. A French cooperative study. Cancer. 1987 Nov 1;60(9):2189–2194. doi: 10.1002/1097-0142(19871101)60:9<2189::aid-cncr2820600913>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
- Berche C., Mach J. P., Lumbroso J. D., Langlais C., Aubry F., Buchegger F., Carrel S., Rougier P., Parmentier C., Tubiana M. Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: first clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen. Br Med J (Clin Res Ed) 1982 Nov 20;285(6353):1447–1451. doi: 10.1136/bmj.285.6353.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brunt L. M., Wells S. A., Jr Advances in the diagnosis and treatment of medullary thyroid carcinoma. Surg Clin North Am. 1987 Apr;67(2):263–279. doi: 10.1016/s0039-6109(16)44183-6. [DOI] [PubMed] [Google Scholar]
- Buraggi G., Callegaro L., Turrin A., Gennari L., Bombardieri E., Mariani G., Deleide G., Dovis M., Gasparini M., Doci R. Immunoscintigraphy of colorectal carcinoma with F (ab')2 fragments of anti-CEA monoclonal antibody. Cancer Detect Prev. 1987;10(5-6):335–345. [PubMed] [Google Scholar]
- Charkes N. D., Vitti R. A., Brooks K. Thallium-201 SPECT increases detectability of thyroid cancer metastases. J Nucl Med. 1990 Feb;31(2):147–153. [PubMed] [Google Scholar]
- Chong G. C., Beahrs O. H., Sizemore G. W., Woolner L. H. Medullary carcinoma of the thyroid gland. Cancer. 1975 Mar;35(3):695–704. doi: 10.1002/1097-0142(197503)35:3<695::aid-cncr2820350323>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
- Clarke S. E., Lazarus C. R., Wraight P., Sampson C., Maisey M. N. Pentavalent [99mTc]DMSA, [131I]MIBG, and [99mTc]MDP--an evaluation of three imaging techniques in patients with medullary carcinoma of the thyroid. J Nucl Med. 1988 Jan;29(1):33–38. [PubMed] [Google Scholar]
- Clarke S. E., Lazarus C., Mistry R., Maisey M. N. The role of technetium-99m pentavalent DMSA in the management of patients with medullary carcinoma of the thyroid. Br J Radiol. 1987 Nov;60(719):1089–1092. doi: 10.1259/0007-1285-60-719-1089. [DOI] [PubMed] [Google Scholar]
- Colombo P., Paganelli G., Magnani P., Songini C., Fazio F., Faglia G. Immunoscintigraphy with anti-chromogranin A antibodies in patients with endocrine/neuroendocrine tumors. J Endocrinol Invest. 1993 Nov;16(10):841–843. doi: 10.1007/BF03348939. [DOI] [PubMed] [Google Scholar]
- Crow J. P., Azar-Kia B., Prinz R. A. Recurrent occult medullary thyroid carcinoma detected by MR imaging. AJR Am J Roentgenol. 1989 Jun;152(6):1255–1256. doi: 10.2214/ajr.152.6.1255. [DOI] [PubMed] [Google Scholar]
- DeLellis R. A., Rule A. H., Spiler I., Nathanson L., Tashjian A. H., Jr, Wolfe H. J. Calcitonin and carcinoembryonic antigen as tumor markers in medullary thyroid carcinoma. Am J Clin Pathol. 1978 Oct;70(4):587–594. doi: 10.1093/ajcp/70.4.587. [DOI] [PubMed] [Google Scholar]
- Dosio F., Magnani P., Paganelli G., Samuel A., Chiesa G., Fazio F. Three-step tumor pre-targeting in lung cancer immunoscintigraphy. J Nucl Biol Med. 1993 Dec;37(4):228–232. [PubMed] [Google Scholar]
- Edington H. D., Watson C. G., Levine G., Tauxe W. N., Yousem S. A., Unger M., Kowal C. D. Radioimmunoimaging of metastatic medullary carcinoma of the thyroid gland using an indium-111-labeled monoclonal antibody to CEA. Surgery. 1988 Dec;104(6):1004–1010. [PubMed] [Google Scholar]
- Fazio F., Paganelli G. Antibody-guided scintigraphy: targeting of the "magic bullet". Eur J Nucl Med. 1993 Dec;20(12):1138–1140. doi: 10.1007/BF00171010. [DOI] [PubMed] [Google Scholar]
- Frank K., Raue F., Lorenz D., Herfarth C., Ziegler R. Importance of ultrasound examination for the follow-up of medullary thyroid carcinoma: comparison with other localization methods. Henry Ford Hosp Med J. 1987;35(2-3):122–123. [PubMed] [Google Scholar]
- Gasparini M., Ripamonti M., Seregni E., Regalia E., Buraggi G. L. Tumor imaging of colo-rectal carcinoma with an anti-CEA monoclonal antibody. Int J Cancer Suppl. 1988;2:81–84. doi: 10.1002/ijc.2910410719. [DOI] [PubMed] [Google Scholar]
- Goldenberg D. M., Kim E. E., DeLand F. H., Bennett S., Primus F. J. Radioimmunodetection of cancer with radioactive antibodies to carcinoembryonic antigen. Cancer Res. 1980 Aug;40(8 Pt 2):2984–2992. [PubMed] [Google Scholar]
- Goodwin D. A., Meares C. F., McCall M. J., McTigue M., Chaovapong W. Pre-targeted immunoscintigraphy of murine tumors with indium-111-labeled bifunctional haptens. J Nucl Med. 1988 Feb;29(2):226–234. [PubMed] [Google Scholar]
- Guerra U. P., Pizzocaro C., Terzi A., Giubbini R., Maira G., Pagliaini R., Bestagno M. New tracers for the imaging of the medullary thyroid carcinoma. Nucl Med Commun. 1989 Apr;10(4):285–295. doi: 10.1097/00006231-198904000-00005. [DOI] [PubMed] [Google Scholar]
- Hilditch T. E., Connell J. M., Elliot A. T., Murray T., Reed N. S. Poor results with technetium-99m (V) DMS and iodine-131 MIBG in the imaging of medullary thyroid carcinoma. J Nucl Med. 1986 Jul;27(7):1150–1153. [PubMed] [Google Scholar]
- Hnatowich D. J., Virzi F., Rusckowski M. Investigations of avidin and biotin for imaging applications. J Nucl Med. 1987 Aug;28(8):1294–1302. [PubMed] [Google Scholar]
- Hoefnagel C. A., Delprat C. C., Zanin D., van der Schoot J. B. New radionuclide tracers for the diagnosis and therapy of medullary thyroid carcinoma. Clin Nucl Med. 1988 Mar;13(3):159–165. doi: 10.1097/00003072-198803000-00003. [DOI] [PubMed] [Google Scholar]
- Kalofonos H. P., Rusckowski M., Siebecker D. A., Sivolapenko G. B., Snook D., Lavender J. P., Epenetos A. A., Hnatowich D. J. Imaging of tumor in patients with indium-111-labeled biotin and streptavidin-conjugated antibodies: preliminary communication. J Nucl Med. 1990 Nov;31(11):1791–1796. [PubMed] [Google Scholar]
- Larson S. M. Radiolabeled monoclonal anti-tumor antibodies in diagnosis and therapy. J Nucl Med. 1985 May;26(5):538–545. [PubMed] [Google Scholar]
- Le Doussal J. M., Martin M., Gautherot E., Delaage M., Barbet J. In vitro and in vivo targeting of radiolabeled monovalent and divalent haptens with dual specificity monoclonal antibody conjugates: enhanced divalent hapten affinity for cell-bound antibody conjugate. J Nucl Med. 1989 Aug;30(8):1358–1366. [PubMed] [Google Scholar]
- Manil L., Boudet F., Motte P., Gardet P., Saccavini J. C., Lumbroso J. D., Schlumberger M., Caillou B., Bazin J. P., Ricard M. Positive anticalcitonin immunoscintigraphy in patients with medullary thyroid carcinoma. Cancer Res. 1989 Oct 1;49(19):5480–5485. [PubMed] [Google Scholar]
- Matzku S., Kirchgessner H., Schmid U., Temponi M., Ferrone S. Melanoma targeting with a cocktail of monoclonal antibodies to distinct determinants of the human HMW-MAA. J Nucl Med. 1989 Mar;30(3):390–397. [PubMed] [Google Scholar]
- Mojiminiyi O. A., Udelsman R., Shepstone B. J., Dudley N. E., Soper N. D. More on [99mTc](V)DMSA scintigraphy in patients with medullary carcinoma of the thyroid. J Nucl Med. 1989 Aug;30(8):1420–1420. [PubMed] [Google Scholar]
- O'Byrne K. J., Hamilton D., Robinson I., Sweeney E., Freyne P. J., Cullen M. J. Imaging of medullary carcinoma of the thyroid using 111In-labelled anti-CEA monoclonal antibody fragments. Nucl Med Commun. 1992 Mar;13(3):142–148. doi: 10.1097/00006231-199203000-00004. [DOI] [PubMed] [Google Scholar]
- Pacini F., Basolo F., Elisei R., Fugazzola L., Cola A., Pinchera A. Medullary thyroid cancer. An immunohistochemical and humoral study using six separate antigens. Am J Clin Pathol. 1991 Mar;95(3):300–308. doi: 10.1093/ajcp/95.3.300. [DOI] [PubMed] [Google Scholar]
- Paganelli G., Magnani P., Zito F., Lucignani G., Sudati F., Truci G., Motti E., Terreni M., Pollo B., Giovanelli M. Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin. Eur J Nucl Med. 1994 Apr;21(4):314–321. doi: 10.1007/BF00947966. [DOI] [PubMed] [Google Scholar]
- Paganelli G., Magnani P., Zito F., Villa E., Sudati F., Lopalco L., Rossetti C., Malcovati M., Chiolerio F., Seccamani E. Three-step monoclonal antibody tumor targeting in carcinoembryonic antigen-positive patients. Cancer Res. 1991 Nov 1;51(21):5960–5966. [PubMed] [Google Scholar]
- Pelagi M., Bisiani C., Gini A., Bonardi M. A., Rosa P., Marè P., Viale G., Grazia Cozzi M., Salvadore M., Zanini A. Preparation and characterization of anti-human chromogranin A and chromogranin B (secretogranin I) monoclonal antibodies. Mol Cell Probes. 1989 Mar;3(1):87–101. doi: 10.1016/0890-8508(89)90039-x. [DOI] [PubMed] [Google Scholar]
- Peltier P., Curtet C., Chatal J. F., Le Doussal J. M., Daniel G., Aillet G., Gruaz-Guyon A., Barbet J., Delaage M. Radioimmunodetection of medullary thyroid cancer using a bispecific anti-CEA/anti-indium-DTPA antibody and an indium-111-labeled DTPA dimer. J Nucl Med. 1993 Aug;34(8):1267–1273. [PubMed] [Google Scholar]
- Reiners C., Eilles C., Spiegel W., Becker W., Börner W. Immunoscintigraphy in medullary thyroid cancer using an 123I- or 111In-labelled monoclonal anti-CEA antibody fragment. Nuklearmedizin. 1986 Dec;25(6):227–231. [PubMed] [Google Scholar]
- Rossi R. L., Cady B., Meissner W. A., Wool M. S., Sedgwick C. E., Werber J. Nonfamilial medullary thyroid carcinoma. Am J Surg. 1980 Apr;139(4):554–560. doi: 10.1016/0002-9610(80)90337-2. [DOI] [PubMed] [Google Scholar]
- Rougier P., Parmentier C., Laplanche A., Lefevre M., Travagli J. P., Caillou B., Schlumberger M., Lacour J., Tubiana M. Medullary thyroid carcinoma: prognostic factors and treatment. Int J Radiat Oncol Biol Phys. 1983 Feb;9(2):161–169. doi: 10.1016/0360-3016(83)90093-7. [DOI] [PubMed] [Google Scholar]
- Schmid K. W., Fischer-Colbrie R., Hagn C., Jasani B., Williams E. D., Winkler H. Chromogranin A and B and secretogranin II in medullary carcinomas of the thyroid. Am J Surg Pathol. 1987 Jul;11(7):551–556. doi: 10.1097/00000478-198707000-00007. [DOI] [PubMed] [Google Scholar]
- Schwerk W. B., Grün R., Wahl R. Ultrasound diagnosis of C-cell carcinoma of the thyroid. Cancer. 1985 Feb 1;55(3):624–630. doi: 10.1002/1097-0142(19850201)55:3<624::aid-cncr2820550325>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
- Seccamani E., Tattanelli M., Mariani M., Spranzi E., Scassellati G. A., Siccardi A. G. A simple qualitative determination of human antibodies to murine immunoglobulins (HAMA) in serum samples. Int J Rad Appl Instrum B. 1989;16(2):167–170. doi: 10.1016/0883-2897(89)90191-8. [DOI] [PubMed] [Google Scholar]
- Siccardi A. G., Buraggi G. L., Callegaro L., Colella A. C., De Filippi P. G., Galli G., Mariani G., Masi R., Palumbo R., Riva P. Immunoscintigraphy of adenocarcinomas by means of radiolabeled F(ab')2 fragments of an anti-carcinoembryonic antigen monoclonal antibody: a multicenter study. Cancer Res. 1989 Jun 1;49(11):3095–3103. [PubMed] [Google Scholar]
- Sinitsyn V. V., Mamontova A. G., Checkneva Y. Y., Shnyra A. A., Domogatsky S. P. Rapid blood clearance of biotinylated IgG after infusion of avidin. J Nucl Med. 1989 Jan;30(1):66–69. [PubMed] [Google Scholar]
- Talerman A., Lindeman J., Kievit-Tyson P. A., Dröge-Droppert C. Demonstration of calcitonin and carcinoembryonic antigen (CEA) in medullary carcinoma of the thyroid (MCT) by immunoperoxidase technique. Histopathology. 1979 Nov;3(6):503–510. doi: 10.1111/j.1365-2559.1979.tb03031.x. [DOI] [PubMed] [Google Scholar]
- Udelsman R., Ball D., Baylin S. B., Wong C. Y., Osterman F. A., Jr, Sostre S. Preoperative localization of occult medullary carcinoma of the thyroid gland with single-photon emission tomography dimercaptosuccinic acid. Surgery. 1993 Dec;114(6):1083–1089. [PubMed] [Google Scholar]
- Vuillez J. P., Peltier P., Caravel J. P., Chetanneau A., Saccavini J. C., Chatal J. F. Immunoscintigraphy using 111In-labeled F(ab')2 fragments of anticarcinoembryonic antigen monoclonal antibody for detecting recurrences of medullary thyroid carcinoma. J Clin Endocrinol Metab. 1992 Jan;74(1):157–163. doi: 10.1210/jcem.74.1.1727816. [DOI] [PubMed] [Google Scholar]
- Zanin D. E., van Dongen A., Hoefnagel C. A., Bruning P. F. Radioimmunoscintigraphy using iodine-131-anti-CEA monoclonal antibodies and thallium-201 scintigraphy in medullary thyroid carcinoma: a case report. J Nucl Med. 1990 Nov;31(11):1854–1855. [PubMed] [Google Scholar]






