Possibilities for formulation of Trastuzumab - radioimunoconjugates

Sterjova, Marija and Dzodic, Predrag and Apostolova, Paulina and Janevik-Ivanovska, Emilija (2016) Possibilities for formulation of Trastuzumab - radioimunoconjugates. In: Workshop “From Molecules to Functionalized Materials“ 1-5 September 2016, Ohrid, Republic of Macedonia.

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Abstract

Trastuzumab (Herceptin®) is a commercially approved humanized IgG1 monoclonal antibody for treatment of HER2 positive breast cancer. Monoclonal antibodies are selective and specific anticancer therapy which are used for conjugation with another dugs, toxins and radioisotopes. In recent years, with the development of radiopharmacy, are synthetized many stable conjugates with various bifunctional chelators (DOTA, DTPA, HYNIC, 1B4M-DTPA, TCMC), for further labeling with radioisotopes.
In order to increase the selectivity of the drugs and toxins and the good clinical results of trastuzumab encouraged many scientists to try to formulate stable conjugates. All radioimmunoconjugates of trastuzumab are in phase of preclinical and clinical examination and allows significant improvement in the general conditions of the patients. For imaging and identification of HER2 positive lesions are developed immunoconjugates labeled with γ and β+ emitters (99mTc-HYNIC-trastuzumab, 111In-DOTA-trastuzumab, 64Ga-DOTA-trastuzumab, 68Ga-DOTA-trastuzumab). In vitro and in vivo investigations shows that conjugates labeled with pure β and α emitters are new promising drugs in treatment of HER2 postitive cancers which allows selective uptake of radioimmunoconjugates by the tumor cells and minimal localizaton in healthy organs. Till now, 177Lu-DOTA-trastuzumab, 90Y-DTPA-trastuzumab, 212Pb-TCMC-trastuzumab, 227Th-DOTA-p-benzyl-trastuzumab and 225Ac-trastuzumab, given good in vivo results and selective internalization in HER2 positive breast, prostate and ovarian cancer cells.
The goal of this examination is to formulate stable freeze dried kit trastuzumab-conjugate with bifunctional chelators (DOTA, DTPA, HYNIC and 1B4M-DTPA) and in vitro chemical characterization and identification. The most stable conjugate will be used for obtaining radioimmunogonjugates with 68Ga and 177Lu and their preclinical in vitro and in vivo biodistribution using animal models.

Item Type: Conference or Workshop Item (Poster)
Subjects: Medical and Health Sciences > Other medical sciences
Divisions: Faculty of Medical Science
Depositing User: Marija Arev
Date Deposited: 13 Sep 2016 11:15
Last Modified: 13 Sep 2016 11:15
URI: https://eprints.ugd.edu.mk/id/eprint/16229

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