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Tumor Biology

, Volume 33, Issue 3, pp 601–606 | Cite as

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

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

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.

Keywords

Pretargeted radioimmunotherapy Medullary thyroid cancer Calcitonin Bispecific antibody Immuno-PET 

Notes

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Françoise Kraeber-Bodéré
    • 1
    • 2
    • 8
  • Pierre-Yves Salaun
    • 3
  • Catherine Ansquer
    • 1
    • 2
  • Delphine Drui
    • 4
  • Eric Mirallié
    • 5
  • Alain Faivre-Chauvet
    • 1
    • 2
  • Jacques Barbet
    • 2
    • 6
  • David M. Goldenberg
    • 7
  • Jean-François Chatal
    • 6
  1. 1.Nuclear Medicine DepartmentUniversity Hospital, ICO René GauducheauNantesFrance
  2. 2.Cancer Research CenterUniversity of Nantes, InsermNantesFrance
  3. 3.Nuclear Medicine DepartmentUniversity HospitalBrestFrance
  4. 4.Endocrinology DepartmentUniversity HospitalNantesFrance
  5. 5.Surgery DepartmentUniversity HospitalNantesFrance
  6. 6.Arronax CyclotronUniversity of NantesNantesFrance
  7. 7.Garden State Cancer CentreCenter for Molecular Medicine and ImmunologyMorris PlainsUSA
  8. 8.Nuclear Medicine DepartmentHôtel Dieu University HospitalNantesFrance

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