Bifunctional chelators for trastuzumab conjugation and successful labeling with radioisotopes

Sterjova, Marija and Dzodic, Predrag and Janevik-Ivanovska, Emilija (2017) Bifunctional chelators for trastuzumab conjugation and successful labeling with radioisotopes. In: 2nd International Scientific Conference of the Faculty of Medical Sciences, Tetovo, Macedonia.

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Bifunctional chelators (BFC) are molecules important for formulation of stable metal complex with targeting biomolecules such as antibodies, peptides or proteins. The chelators are covalently attached to the biomolecules on the one side and on the other coordinates to the radioisotopes. The goal is to produce a radiopharmaceuticals with pharmacokinetic and pharmacodynamic stability, without degradation of the complex in the physiological conditions and releasing of metal ion. The choice of the chelators depends of the type of radioactive isotope that will be used.
Many efforts have been made in order to formulate a stable immunoconjugates of anti-HER2 monoclonal antibody trastuzumab with different types of BFC for further labeling with radioisotopes for imaging or radiotherapy of HER2 positive metastatic breast cancer. Succinimidyl-hydrazinonicotinamide (HYNIC) is important for trastuzumab conjugation and labeling with 99mTc and 188Re. For formulation of radioimmunoconjugates with 212Pb 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraaza-cyclododecane (TCMC) have been used as a chelator. The most commonly used BFC are 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and diethylene triamine pentaacetic acid (DTPA). Preclinical characterization was made of 111In radiolabeled trastuzumab, previously conjugated with DTPA as a chelator. DTPA was used for trastuzuamab conjugation in a case of labeling with β emitters 86Y and 90Y. Chelating agent DOTA is significant for formulation of trastuzumab-radioimunoconjugates with gamma emitter 67Ga, and potent therapeutic agents with β- emitter 177Lu and α emitter 225Ac.
The aim of our study is to formulate a stable immunoconjugates of trastuzumab with DTPA, DOTA and DTPA derivate 1B4M-DTPA (2-(4-isothiocyanatobenzyl)-6-methyl-diethylene-triaminepentaacetic acid) for further labeling with 90Y and 177Lu.

Item Type: Conference or Workshop Item (Speech)
Subjects: Medical and Health Sciences > Basic medicine
Divisions: Faculty of Medical Science
Depositing User: Marija Arev
Date Deposited: 01 Nov 2017 13:43
Last Modified: 01 Nov 2017 13:43

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