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

  • Research Article
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Tumor Biology

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.

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Authors and Affiliations

  1. Nuclear Medicine Department, University Hospital, ICO René Gauducheau, Nantes, France

    Françoise Kraeber-Bodéré, Catherine Ansquer & Alain Faivre-Chauvet

  2. Cancer Research Center, University of Nantes, Inserm, Nantes, France

    Françoise Kraeber-Bodéré, Catherine Ansquer, Alain Faivre-Chauvet & Jacques Barbet

  3. Nuclear Medicine Department, University Hospital, Brest, France

    Pierre-Yves Salaun

  4. Endocrinology Department, University Hospital, Nantes, France

    Delphine Drui

  5. Surgery Department, University Hospital, Nantes, France

    Eric Mirallié

  6. Arronax Cyclotron, University of Nantes, Nantes, France

    Jacques Barbet & Jean-François Chatal

  7. Garden State Cancer Centre, Center for Molecular Medicine and Immunology, Morris Plains, NJ, USA

    David M. Goldenberg

  8. Nuclear Medicine Department, Hôtel Dieu University Hospital, 1 place Ricordeau, 44093, Nantes, France

    Françoise Kraeber-Bodéré

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  1. Françoise Kraeber-Bodéré
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  2. Pierre-Yves Salaun
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  3. Catherine Ansquer
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  7. Jacques Barbet
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  8. David M. Goldenberg
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  9. Jean-François Chatal
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Correspondence to Françoise Kraeber-Bodéré.

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Kraeber-Bodéré, F., Salaun, PY., Ansquer, C. et al. Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC). Tumor Biol. 33, 601–606 (2012). https://doi.org/10.1007/s13277-012-0359-6

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  • DOI: https://doi.org/10.1007/s13277-012-0359-6

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