Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Tumor Biology
Published in: Tumor Biology 3/2012

01-06-2012 | Research Article

Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC)

Authors: Françoise Kraeber-Bodéré, Pierre-Yves Salaun, Catherine Ansquer, Delphine Drui, Eric Mirallié, Alain Faivre-Chauvet, Jacques Barbet, David M. Goldenberg, Jean-François Chatal

Published in: Tumor Biology | Issue 3/2012

Login to get access

Abstract

Prognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival, based on prognostic factors, such as serum calcitonin doubling time (Ct DT). Pretargeted radioimmunotherapy (pRAIT) is a novel targeted radionuclide therapy, using a bispecific monoclonal antibody (BsMAb) and a radiolabeled bivalent hapten, designed to improve the therapeutic index and to deliver increased tumor-absorbed doses to relatively radioresistant solid tumors. Pretargeting has demonstrated a more favorable therapeutic index and clinical efficacy than directly labeled anti-carcinoembryonic antigen (CEA) MAb in preclinical MTC models. Moreover, two phase I/II clinical trials assessing anti-CEA × anti-DTPA-indium BsMAb (murine F6x734 and chimeric hMN14x734) with 131I-di-DTPA-indium showed encouraging therapeutic results in progressive, metastatic, MTC patients, with an improved survival in intermediate- and high-risk (pre-pRAIT Ct DT, <2 years) patients, as compared to contemporaneous untreated patients (median overall survival, 110 months vs 61 months; P < 0.030). pRAIT efficacy has been recently confirmed in a prospective multicenter phase II study assessing hMN14x734 and 131I-di-DTPA-indium in rapidly progressive MTC patients. New pRAIT compounds are now available with fully humanized, recombinant, trivalent BsMAb (anti-CEA TF2) and histamine–succinyl–glutamine (HSG) peptides. The HSG peptide allows easy and stable labeling with different radiometals, such as 177Lu or 90Y beta-emitters having favorable physical features for pRAIT or 68Ga and 18F positron-emitters, allowing the development of a highly sensitive and specific immuno-positron emission tomography method in MTC or other CEA-positive tumors.
Literature
1.
Hundahl SA, Fleming ID, Fremgen AM, et al. 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.PubMedCrossRef
2.
Schlumberger M, Carlomagno F, Baudin E, et al. New therapeutic approaches to treat medullary thyroid carcinoma. Nat Clin Pract Endocrinol Metab. 2008;4:22–32.PubMedCrossRef
3.
Tubiana M, Milhaud G, Coutris G, Lacour J, Parmentier C, Bok B. Medullary carcinoma and thyrocalcitonin. Br Med J. 1968;4:87–9.PubMedCrossRef
4.
Machens A, Schneyer U, Holzhausen HJ, Dralle H. Prospects of remission in medullary thyroid carcinoma according to basal calcitonin level. J Clin Endocrinol Metab. 2005;90:2029–34.PubMedCrossRef
5.
Fialkowski E, DeBenedetti M, Moley J. Long-term outcome of reoperations for medullary thyroid carcinoma. World J Surg. 2008;32:754–65.PubMedCrossRef
6.
Bergholm U, Bergström R, Ekbom A. Long-term follow-up of patients with medullary thyroid carcinoma of the thyroid. Cancer. 1997;79:132–8.PubMedCrossRef
7.
Juweid M, Sharkey RM, Behr T, et al. Radioimmunotherapy of medullary thyroid cancer with 131I-labeled anti-CEA antibodies. J Nucl Med. 1996;37:905–11.PubMed
8.
Juweid ME, Hajjar G, Swayne LC, et al. Phase I/II trial of (131)I-MN-14F(ab)2 anti-carcinoembryonic antigen monoclonal antibody in the treatment of patients with metastatic medullary thyroid carcinoma. Cancer. 1999;85:1828–42.PubMedCrossRef
9.
Juweid ME, Hajjar G, Stein R, et al. Initial experience with high-dose radioimmunotherapy of metastatic medullary thyroid cancer using 131I-MN-14F(ab)2 anti-carcinoembryonic antigen MAb and AHSCR. J Nucl Med. 2000;41:93–103.PubMed
10.
Goldenberg DM, Sharkey RM, Paganelli G, et al. Antibody pretargeting advances cancer radioimmunodetection and radioimmunotherapy. J Clin Oncol. 2006;24:823–34.PubMedCrossRef
11.
Modigliani E, Cohen R, Campos JM, et al. Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: results in 899 patients. Clin Endocrinol. 1998;48:265–73.CrossRef
12.
Miccoli P, Minuto MN, Ugolini C, et al. Clinically unpredictable prognostic factors in the outcome of medullary thyroid cancer. Endocr Relat Cancer. 2007;14:1099–105.PubMedCrossRef
13.
Kebebew E, Ituarte PH, Siperstein AE, Duh QY, Clark OH. Medullary thyroid carcinoma. Clinical characteristics, treatment, prognostic factors, and a comparison of staging systems. Cancer. 2000;88:1139–48.PubMedCrossRef
14.
Byar DP, Green SB, Dor P, et al. A prognostic index for thyroid carcinoma. A study of the E.O.R.T.C. Thyroid Cancer Cooperative Group. Eur J Cancer. 1979;15:1033–41.PubMedCrossRef
15.
Elisei R, Cosci B, Romei C, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab. 2008;93:682–7.PubMedCrossRef
16.
Ito Y, Yoshida H, Tomoda C. Expression of cdc25B and cdc25A in medullary thyroid carcinoma: cdc25B expression level predicts a poor prognosis. Cancer Lett. 2005;229:291–7.PubMedCrossRef
17.
Tisell LE, Oden A, Muth A, et al. The Ki67 index a prognostic marker in medullary thyroid carcinoma. Br J Cancer. 2003;89:2093–7.PubMedCrossRef
18.
Barbet J, Campion L, Kraeber-Bodéré F, et al. Prognostic impact of serum calcitonin and carcinoembryonic antigen doubling-times in patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2005;90:6077–84.PubMedCrossRef
19.
Mirallié E, Vuillez JP, Bardet S, et al. High frequency of bone/bone marrow involvement in advanced medullary thyroid cancer. J Clin Endocrinol Metab. 2005;90:779–88.PubMedCrossRef
20.
Oudoux A, Salaun PY, Bournaud C, et al. Sensitivity and prognostic value of positron emission tomography with F-18-fluorodeoxyglucose and sensitivity of immunoscintigraphy in patients with medullary thyroid carcinoma treated with anticarcinoembryonic antigen-targeted radioimmunotherapy. J Clin Endocrinol Metab. 2007;92:4590–7.PubMedCrossRef
21.
American Thyroid Association Guidelines Task Force, Kloos RT, Eng C, et al. Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19:565–612.PubMedCrossRef
22.
Luster M, Karges W, Zeich K, et al. Clinical value of 18-fluorine-fluorodihydroxyphenylalanine positron emission tomography/computed tomography in the follow-up of medullary thyroid carcinoma. Thyroid. 2010;20:527–33.PubMedCrossRef
23.
Karacay H, Sharkey RM, McBride WJ, et al. Optimization of hapten-peptide labeling for pretargeted immunoPET of bispecific antibody using generator-produced 68Ga. J Nucl Med. 2011;52:555–9.PubMedCrossRef
24.
McBride WJ, Sharkey RM, Karacay H, et al. A novel method of 18F radiolabeling for PET. J Nucl Med. 2009;50:991–8.PubMedCrossRef
25.
Schoffelen R, Sharkey RM, Goldenberg DM, et al. Pretargeted immuno-positron emission tomography imaging of carcinoembryonic antigen-expressing tumors with a bispecific antibody and a 68Ga- and 18F-labeled hapten peptide in mice with human tumor xenografts. Mol Cancer Ther. 2010;9:1019–27.PubMedCrossRef
26.
McBride WJ, Zanzonico P, Sharkey RM, et al. Bispecific antibody pretargeting PET (immunoPET) with an 124I-labeled hapten-peptide. J Nucl Med. 2006;47:1678–88.PubMed
27.
Hosono M, Hosono M, Kraeber-Bodéré F, et al. Biodistribution and dosimetry study in medullary thyroid cancer xenograft using bispecific antibody and iodine-125-labeled bivalent hapten. J Nucl Med. 1998;39:1608–13.PubMed
28.
Kraeber-Bodéré F, Faivre-Chauvet A, Sai-Maurel C, et al. Comparative toxicity and efficacy of one- and two-step (bipecific antibody and bivalent hapten) radioimmunotherapy in CEA-producing medullary thyroid cancer. J Nucl Med. 1999;40:198–204.PubMed
29.
Kraeber-Bodere F, Bardet S, Hoefnagel CA, et al. Radioimmunotherapy in medullary thyroid cancer using bispecific antibody and iodine 131-labeled bivalent hapten: preliminary results of a phase I/II clinical trial. Clin Cancer Res. 1999;5:3190–8.
30.
Kraeber-Bodere F, Faivre-Chauvet A, Ferrer L, et al. Pharmacokinetics and dosimetry studies for optimisation of carcinoembryonic antigen × anti-hapten bispecific antibody mediated pretargeting of iodine-131-labeled hapten in a phase I radioimmunotherapy trial. Clin Cancer Res. 2003;9:3973–81.
31.
Kraeber-Bodere F, Rousseau C, Bodet-Milin C, et al. Targeting, toxicity and efficacy of 2-step, pretargeted radioimmunotherapy using a chimeric bispecific antibody and 131-I-labeled bivalent hapten in a phase I optimisation clinical trial. J Nucl Med. 2006;47:247–55.PubMed
32.
Chatal JF, Campion L, Kraeber-Bodéré F, et al. Survival improvement in patients with medullary thyroid carcinoma who undergo pretargeted anti-carcinoembryonic-antigen radioimmunotherapy: a collaborative study with the French Endocrine Tumor Group. J Clin Oncol. 2006;24:1705–11.PubMedCrossRef
33.
Salaun PY, Bournaud C, Bardet S, et al. Pretargeted radioimmunotherapy (pRAIT) in progressive metastatic medullary thyroid cancer (MTC): results of a phase II trial. Annual Congress of Society of Nuclear Medicine, San Antonio. 2011.
34.
Kraeber-Bodéré F, Saï-Maurel C, Campion L, et al. Enhanced antitumor activity of combined pretargeted radioimmunotherapy and paclitaxel in medullary thyroid cancer xenograft. Mol Cancer Ther. 2002;1:267–74.PubMed
35.
Kraeber-Bodéré F, Bodet-Milin C, Niaudet C, et al. Comparative toxicity and efficacy of combined radioimmunotherapy and antiangiogenic therapy in carcinoembryonic antigen-expressing medullary thyroid cancer xenograft. J Nucl Med. 2010;51:624–31.PubMedCrossRef
36.
Salaun PY, Bodet-Milin C, Frampas E, et al. Toxicity and efficacy of combined radioimmunotherapy and bevacizumab in a mouse model of medullary thyroid carcinoma. Cancer. 2010;116:1053–8.PubMedCrossRef
37.
Iten F, Müller B, Schindler C, et al. Response to [90Ytrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin Cancer Res. 2007;13:6696–702.PubMedCrossRef
38.
Gross DJ, Munter G, Bitan M, et al. The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R. Endocr Relat Cancer. 2006;13:535–40.PubMedCrossRef
39.
de Groot JWB, Zonnenberg BA, Quarles van Ufford-Mannesse P, et al. A phase II trial of imatinib therapy for metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab. 2007;92:3466–9.PubMedCrossRef
40.
Frank-Raue K, Fabel M, Delorme S, et al. Efficacy of imatinib mesylate in advanced medullary thyroid carcinoma. Eur J Endocrinol. 2007;157:215–20.PubMedCrossRef
41.
Schlumberger MJ, Elisei R, Bastholt L, et al. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer. J Clin Oncol. 2009;27:3794–801.PubMedCrossRef
42.
Lam ET, Ringel MD, Kloos RT, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010;28:2323–30.PubMedCrossRef
43.
Wells Jr SA, Gosnell JE, Gagel RF, et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol. 2010;28:767–72.PubMedCrossRef
44.
Wells SA, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012;30:134–41.PubMedCrossRef
45.
Goldenberg DM, Rossi EA, Sharkey RM, et al. Multifunctional antibodies by the Dock-and-Lock method for improved cancer imaging and therapy by pretargeting. J Nucl Med. 2008;49:158–63.PubMedCrossRef
46.
Rossi EA, Goldenberg DM, Cardillo TM, et al. Stably tethered multifunctional structures of defined composition made by the dock and lock method for use in cancer targeting. Proc Natl Acad Sci U S A. 2006;103:6841–6.PubMedCrossRef
47.
Schoffelen R, van der Graaf WT, Franssen G, et al. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice. J Nucl Med. 2010;51:1780–7.PubMedCrossRef
Metadata
Title
Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC)
Authors
Françoise Kraeber-Bodéré
Pierre-Yves Salaun
Catherine Ansquer
Delphine Drui
Eric Mirallié
Alain Faivre-Chauvet
Jacques Barbet
David M. Goldenberg
Jean-François Chatal
Publication date
01-06-2012
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2012
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-012-0359-6

Other articles of this Issue 3/2012

Tumor Biology 3/2012 Go to the issue

Research Article

Dosimetry results suggest feasibility of radioimmunotherapy using anti-CD138 (B-B4) antibody in multiple myeloma patients

Research Article

mTORC1 inhibition and ECM–cell adhesion-independent drug resistance via PI3K–AKT and PI3K–RAS–MAPK feedback loops

Research Article

DM-1, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate: a curcumin analog with a synergic effect in combination with paclitaxel in breast cancer treatment

Research Article

Long-term adaptation of the human lung tumor cell line A549 to increasing concentrations of hydrogen peroxide

Research Article

Nuclisome—targeting the tumor cell nucleus

Research Article

Vascular endothelial growth factor A gene (VEGFA) polymorphisms and expression of VEGFA gene in lung cancer patients of Kashmir Valley (India)
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits