Development and characterization of DTPA-trastuzumab conjugates for radiolabeling with Tc-99m: A radiopharmaceutical for HER2/neu breast cancer

HER2/neu expressing cancers constitute 30% of all breast cancers. Trastuzumab, a monoclonal antibody, is widely used for the treatment of HER2/neu expressing breast cancers. The aim of this study was to conjugate trastuzumab with a bifunctional chelator, cyclic Diethylene triamine-pentaacetic anhydride (cDTPAA) for radiolabeling with Tc-99m to develop a radio-pharmaceutical for assessment of HER2/neu status for treatment planning and response monitoring post trastuzumab treatment. cDTPAA was conjugated to trastuzumab at various molar ratios (10:1–100:1). The conjugates were purified and characterized for the integrity and number of chelator molecules conjugated. Radiolabeling of cDTPAA-trastuzumab conjugates was done with Tc-99 m and labeling parameters were studied. The quality control of the radiolabeled preparation was carried out by radio thin layer chromatography (TLC). Endotoxin estimation and sterility test were performed. Biodistribution studies were carried out at different time intervals (1 h, 6 h and 12 h) post intravenous injections in normal rats. The average number of molecules conjugated varied from 0.75 to 7.5 for the different molar ratios experimented. Maximum radiolabeling yield obtained was 90%. Post purification radiochemical purity was >95%. The biodistribution studies showed high activity in liver, kidney and blood retention up to the period of 12 h.

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