Positron Emission Tomography Imaging of Tumor Angiogenesis with a 66Ga-Labeled Monoclonal Antibody

The goal of this study was to develop a Ga-66-based positron emission tomography (PET) tracer for noninvasive imaging of CD 105 expression during tumor angiogenesis, a hallmark of cancer. Ga-66 was produced using a cyclotron with Zn-nat or isotopically enriched Zn-66 targets. TRC105, a chimeric anti-CD105 monoclonal antibody, was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with Ga-66. No difference in CD105 binding affinity or specificity was observed between TRC105 and NOTA-TRC105 based on flow cytometry analysis. Reactivity of Ga-66 for NOTA, corrected to the end of bombardment, was between 74 and 222 GBq/mu mol for both target enrichments with <2 ppb of cold gallium. Ga-66-labeling was achieved with >80% radiochemical yield. Serial PET imaging revealed that the murine breast cancer 4T1 tumor uptake of Ga-66-NOTA-TRC105 was 5.9 +/- 1.6, 8.5 +/- 0.6, and 9.0 +/- 0.6% ID/g at 4, 20, and 36 h postinjection, respectively (n = 4). At the last time point, tumor uptake was higher than that of all organs, which gave excellent tumor contrast with a tumor/muscle ratio of 10.1 +/- 1.1. Biodistribution data as measured by gamma counting were consistent with the PET findings. Blocking experiment, control studies with Ga-66-NOTA-cetuximab, as well as ex vivo histology all confirmed the in vivo target specificity of Ga-66-NOTA-TRC105. Successful PET imaging with high specific activity Ga-66 (>700 GBq/mu mol has been achieved) as the radiolabel opens many new possibilities for future PET research with antibodies or other targeting ligands.