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

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 (131)I-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 (131)I-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 (177)Lu or (90)Y beta-emitters having favorable physical features for pRAIT or (68)Ga and (18)F positron-emitters, allowing the development of a highly sensitive and specific immuno-positron emission tomography method in MTC or other CEA-positive tumors.
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https://hal.univ-brest.fr/hal-00932128
Contributor : Ghislaine Calvez <>
Submitted on : Thursday, January 16, 2014 - 1:10:45 PM
Last modification on : Friday, June 19, 2020 - 3:08:41 AM

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Françoise Kraeber-Bodéré, Pierre-Yves Salaun, Catherine Ansquer, Delphine Drui, Eric Mirallié, et al.. Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC).. Tumor Biology, Springer Verlag, 2012, 33 (3), pp.601-6. ⟨10.1007/s13277-012-0359-6⟩. ⟨hal-00932128⟩

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