production and preclinical evaluation of the 67ga-chx-a-dtpa-trastuzumab for her2+ breast cancer spect imaging

Radiolabeled monoclonal antibodies have shown great promise for cancer diagnosis and therapy. approximately 15% to 20% of breast cancers exhibit an overexpression of a growth-promoting protein known as her2. in the present study, trastuzumab was conjugated with chx-a-dtpa (macrocyclics b-355), the average number of the chelator conjugated per mab was calculated and total concentration was determined by spectrophotometrically. chx-a-dtpa–trastuzumab was labeled with 67ga (10 mci, 375 mbq) then radiochemical purity and immunoreactivity by skbr3 cell line and serum stability of 67ga-chx-a-dtpa-trastuzumab were determined. the biodistribution studies was performed in female sprague dowley rat (67ga–chx-a-dtpa–trastuzumab i.v., 200 microl, 200±20 mci, 35±5 μg mab , 4, 24, 48 and 72 h). 67ga-chx-a-dtpa-trastuzumab was prepared (rcp>98% ± 0.5, specific activity 4.1±0.7 μci/μg). conjugation reaction (c/a) was 4.1±1.2. labeling yield was 92.5% ± 2.1. immunoreaction of 67ga-chx-a-dtpa- trastuzumab complex towards her2 antigen was determined by ria and the complex showed high immunoreactivity towards her2. in vitro stability showed more than 91%±2.6 in the pbs and 81%±1.8 in the serum over 24 h. the immunoreactivity of the radiolabeled anti-her2 towards skbr3 cell line was done by using lindmo assay protocol which was found to be 0.84. the biodistribution of 67ga–chx-a-dtpa-trastuzumab complex in normal sprague dowley rat at 4, 24, 48, and 72 h after intravenous administration, expressed as (%id/g). biodistribution studies at 24 and 48 h post-injection revealed the similar pattern to the other radiolabeled anti-her2 immunoconjugates