Enhanced Tumor-to-Background Contrast with [⁵²Mn]Mn-BPPA-Bevacizumab VEGF-Targeted Immuno-PET in Cervical Cancer

Background/Objectives: Radiolabeled bevacizumab-based immuno-PET tracers enable a non-invasive quantification of VEGF-A expression in gynecologic malignancies. While the previously reported [⁵²Mn]Mn-DOTAGA-bevacizumab demonstrated selective VEGF-A-targeted uptake in a KB-3-1 cervix carcinoma mouse model, further improvements in chelator stability and tumor-to-background contrast remain desirable. The recently developed BPPA chelator exhibits exceptionally high Mn(II) complex stability and favorable radiolabeling characteristics. This study aimed to characterize the in vivo biodistribution of [⁵²Mn]Mn-BPPA-bevacizumab, and to compare the tumor-to-background ratios of [⁵²Mn]Mn-BPPA-bevacizumab with the previously published values of [⁵²Mn]Mn-DOTAGA-bevacizumab in VEGF-A-expressing cervix carcinoma. Methods: Female KB-3-1 tumor-bearing CB17 SCID mice underwent PET/MRI imaging following intravenous administration of [⁵²Mn]Mn-BPPA-bevacizumab. SUV_mean values were measured in various organs and in the subcutaneously injected tumor, and tumor-to-organ ratios were calculated at various time points up to 10 days post-injection. Results: [⁵²Mn]Mn-BPPA-bevacizumab demonstrated sustained tumor uptake, with tumor SUVmean values increasing from approximately 1.0 at 4 h to peak values of approximately 2.4-2.5 at 72 h post-injection. Tumor-to-background ratios increased progressively over time and were significantly higher for [⁵²Mn]Mn-BPPA-bevacizumab compared with previously reported [52Mn]Mn-DOTAGA-bevacizumab, particularly for tumor-to-blood, tumor-to-liver and tumor-to-lung ratios at later imaging time points (p < 0.0001). Conclusions: The novel [⁵²Mn]Mn-BPPA-bevacizumab tracer exhibits satisfactory in vitro and in vivo stability for PET imaging, high VEGF-A-specific tumor uptake, and markedly improved tumor-to-background ratios compared to the previously published DOTAGA-based probe. These results position [⁵²Mn]Mn-BPPA-bevacizumab as a highly promising next-generation immuno-PET agent for imaging VEGF-A-expressing gynecologic malignancies and for guiding anti-angiogenic therapies.