Synthesis and in vivo evaluation of a polar [F]BODIPY-Tetrazine as a pretargeted bimodal imaging agent.

Fluorescence intraoperative guided surgery (FIGS) allows surgeons to resect tumors more completely - without damaging or removing healthy tissue. We have recently shown that pretargeted FIGS can improve contrast between malignances and healthy tissue. Therefore, pretargeted FIGS has the potential to improve conventional FIGS. In this work, we aimed to develop a FIGS agent that could simultaneously be imaged by positron emission tomography (PET). Such possibility would allow determination of the time point with the highest tumor-to-background ratio. Consequently, surgeons would be able to decide when to perform the surgery with the highest precision. PET has the advantage to be non-invasive and as such, easily be transferrable into a clinical setting. F-Radiolabeling of our BODIPY based pretargeted FIGS imaging agent 9 succeeded via a pseudo-halogen exchange reaction in a radiochemical conversion of approximately 15 % and a radiochemical yield of 3-7 %. However, [F]9 exhibited low stability in PBS suggesting it not be suited to reveal the best timepoint when pretargeted FIGS should be initiated. This study shows that F-labeling of BODIPY via pseudo-halogen exchange is possible, but the stability of the [F]BF core is limited. Consequently, application of similar labeling strategies for other in vivo applications should be carefully considered.