An efficient method for direct conversion of fluorescent probe into PET/fluorescent probe

Objectives Although fluorescent dyes could be used for PET/optical probe construction, the procedure generally involves a separate introduction of fluorescent tag and radioactive tag. Based on our newly developed fluoride exchange approach, in this study, a simple and fast method was developed to directly convert BODIPY dye conjugated fluorescent probe into PET/fluorescent probe.

Methods The BODIPY dyes were conjugated to peptide (BODIPY-RGD) or organic inhibitor (BODIPY-NB1) respectively to obtain the fluorescent probes first. Various reaction temperatures, times, solvents, and additives, were explored to optimize the labeling reaction with 18F. Radio-HPLC was used to monitor the reaction progress.

Results In the presence of Lewis acids, both BODIPY-RGD and BODIPY-NB1 can be radiolabeled in the matter of minutes with azeotropically dried 18F-fluoride in good yields. The 18F-BODIPY-RGD was obtained in 20% labeling yield based on 18F-fluoride. Due to the cationic and lipophilic nature of 18F-BODIPY-RGD, this agent showed a strong PET signal from the kidney and liver of the mice. 18F-BODIPY-NB1 was obtained in 80% labeling yield. As shown in the figure, no apparent bone uptake was observed up to 3h p.i, which indicated its good stability in vivo.

Conclusions We discovered that Lewis acids can be used to promote the 18F-labeling of BODIPY-conjugates in high efficiency. Our approach allows the direct conversion of a fluorescent probe into PET/fluorescence probe.

Research Support This research was supported by the American Cancer Society (MRSG-12-034-01-CCE) and Wright foundation. We would also like to thank Dr. Neamati's group for providing the BODIPY-NB1 compound.