Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC).
Tumour Biol
; 33(3): 601-6, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-22396039
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Glândula Tireoide
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Radioimunoterapia
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article