Photoradiosynthesis of 68Ga-Labeled HBED-CC-Azepin-MetMAb for Immuno-PET of c-MET Receptors

In an alternative approach for radiotracer design, a photoactivatable HBED-CC-PEG(3)-ArN3 chelate was synthesized and photoconjugated to the anti-c-MET antibody MetMAb (onartuzumab). Photoconjugation gave the functionalized protein HBED-CC-azepin-MetMAb with a photochemical conversion of 18.5 +/- 0.5% (n = 2) which was then radiolabeled with Ga-68(3+) ions. The purified and formulated [Ga-68]GaHBED-CC-azepin-MetMAb radio-tracer was evaluated in vitro and in vivo. Standard stability tests and cellular binding assays confirmed that the radiotracer remained radiochemically pure and immunoreactive after photochemical conjugation. [Ga-68]GaHBED-CC-azepin-MetMAb showed specific uptake in c-MET-positive MKN-45 (high-expression) and PC-3 (low/moderate expression) tumors with tumor-associated activities at 6 h post-administration of 10.33 +/- 1.27 (n = 5) and 3.88 +/- 1.27 (n = 3) %ID/g, respectively. In competitive blocking experiments, MKN-45 tumor uptake was reduced by approximately 55% (P-value <0.001 compared with nonblocked experiments) confirming specific radiotracer binding to c-MET in vivo. Radiochemical, cellular, and in vivo experiments confirmed that the photo-radiochemical approach is a viable tool to synthesize new radiotracers for immuno-PET.