Synthesis and stability test of radioimmunoconjugate 177Lu-DOTA-F(ab′)2-trastuzumab for theranostic agent of HER2 positive breast cancer

作者: Sandra Hermanto , Ratna Dini Haryuni , Martalena Ramli , Abdul Mutalib , Sumi Hudiyono

DOI: 10.1016/J.JRRAS.2016.07.001

关键词:

摘要: The use of trastuzumab as intact IgG labeling radionuclide for HER2 positive breast cancer theranostic agent is not ideal because it slowly eliminated from the blood and normal tissues resulting in low tumor/blood (T/B) tumor/normal tissue (T/NT) ratios. To overcome this limitation, we developed F(ab′)2 fragments radiolabeling by β γ-particle Lutetium-177. F(ab)2 were produced digestion (Herceptin) with pepsin 18 h at 37 °C. fragment fractionated PD-10 column, followed conjugation 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA) a metal chelator 177LuCl3. Molecular weight was calculated LCMS (Liquid Chromatography Mass Spectroscopy) radiochemical purity evaluated ITLC-SG (Instan Thin Layer Chromatography). Our study showed that generated fractions >98% molecular 98.35 kDa. average numbers pSCN-Bn-DOTA chelates per antibody 5.03 ± 1.5 optimum reactions performed molar ratio 20:1 (chelator to antibody). stability test radioimmunoconjugate human serum albumin (HSA) °C 91.96 0.26% after 96 storage. This indicated relatively stable when applied body's physiological condition.

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