Cetuximab was the first monoclonal antibody targeting EGFR that was approved by the FDA for the treatment of metastatic colorectal and head & neck cancer. We previously showed that Cu-64 labeled DOTA-cetuximab is a potential tracer for PET imaging of EGFR-positive tumors; however, poor in vivo stability caused suboptimal tumor:non-tumor ratios.  Here we compare DOTA to CB-TE1A1P, a cross-bridged macrocyclic chelator that allows for Cu-64 radiolabeling at lower temperatures. Biodistribution of this new compound in nude mice bearing human colorectal tumors (HCT116) was compared with 64Cu-DOTA-cetuximab, and showed improved blood clearance and lower liver uptake. The tumor: non-tumor ratios for Cu-64-CB-TE1A1P-cetuximab at 24 and 48 h are significantly higher than 64Cu-DOTA-cetuximab. A drawback of CB-TE1A1P-cetuximab is that low specific activities are achieved with Cu-64 labeling due to conjugation techniques.  Novel click-based methodologies for improving specific activity will be discussed.

Strategies for improving specific activity and biodistribution of copper-64-labeled anti-EGFR antibody cetuximab

243rd National Meeting (2012)

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