title: 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.
authors.affiliation: Nuclear Medicine Department, University Hospital, ICO René Gauducheau, Nantes, France. francoise.bodere@chu-nantes.fr
authors.forename: Françoise
authors.initials: F
authors.lastname: Kraeber-Bodéré
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Salaun
authors.forename: Catherine
authors.initials: C
authors.lastname: Ansquer
authors.forename: Delphine
authors.initials: D
authors.lastname: Drui
authors.forename: Eric
authors.initials: E
authors.lastname: Mirallié
authors.forename: Alain
authors.initials: A
authors.lastname: Faivre-Chauvet
authors.forename: Jacques
authors.initials: J
authors.lastname: Barbet
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Chatal
mesh_terms: D000818:Animals; D018278:Carcinoma, Neuroendocrine; D003131:Combined Modality Therapy; D006801:Humans; D009362:Neoplasm Metastasis; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016499:Radioimmunotherapy; D013964:Thyroid Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000532:radiotherapy*
chemical_list: D047428:Protein Kinase Inhibitors