Radiolabelled Cyclodextrins for the Positron Emission Tomography Imaging of Breast Cancer: Preclinical Perspectives

Given the increasing incidence and mortality of breast cancer, the development of target‐specific imaging probes for early disease detection seems straightforward. Prostaglandin E2 (PGE2) and its receptors have a crucial role in tumor angiogenesis; therefore, radiolabelled cyclodextrins targeting such biomolecules may serve as selective vectors for positron emission tomography (PET) imaging of breast cancer. Herein, we aimed to monitor PGE2 production in MDA‐MB‐HER2‐positive and 4 T1 triple‐negative breast cancer xenografts using 68 Ga‐labeled randomly methylated beta cyclodextrin (RAMEB) and 2‐hydroxypropyl‐beta‐cyclodextrin (HPβCD) and PET technique. After the injection of [ 68 Ga]Ga‐NODAGA‐HPβCD and [ 68 Ga]Ga‐DOTAGA‐RAMEB, CB17 SCID mice bearing breast tumors underwent weekly PET imaging with subsequent quantitative data assessment and ex vivo biodistribution studies. Both cyclodextrin compounds were suitable to identify the tumors, though tracer accumulation varied with tumor size. Significantly higher [ 68 Ga]Ga‐NODAGA‐HPβCD uptake was observed in the MDA‐MB‐HER2+ tumors across all sizes (small, medium, and large‐sized) compared to the 4 T1 counterparts. In contrast, [ 68 Ga]Ga‐DOTAGA‐RAMEB accumulated to a greater extent in small and midsized 4 T1 tumors in comparison with size‐matched MDA‐MB‐HER2+ tumors, while it showed higher uptake in the large HER2+ lesions than in 4 T1. The presented results indicate notable radioactivity in both 4 T1 and MDA‐MB‐HER2+ tumors designating [ 68 Ga]Ga‐DOTAGA‐RAMEB and [ 68 Ga]Ga‐NODAGA‐HPβCD as effective PET probes for the identification of breast cancer.