Room Temperature Al18F Labeling of 2-Aminomethylpiperidine-Based Chelators for PET Imaging

Positron emission tomography (PET) is a non‐invasive molecular imaging technology that is constantly expanding, with a high demand for specific antibody‐derived imaging probes. The use of tracers based on temperature‐sensitive molecules (i. e. Fab, svFab, nanobodies) is increasing and has led us to design a class of chelators based on the structure of 2‐aminomethylpiperidine (AMP) with acetic and/or hydroxybenzyl pendant arms (2‐AMPTA, NHB‐2‐AMPDA, and 2‐AMPDA‐HB), which were investigated as such for {Al18F}2+‐core chelation efficiency. All the compounds were characterized by HPLC‐MS analysis and NMR spectroscopy. The AlF‐18 labeling reactions were performed under various conditions (pH/temperature), and the radiolabeled chelates were purified and characterized by radio‐TLC and radio‐HPLC. The stability of labeled chelates was investigated up to 240 min in human serum (HS), EDTA 5 mM, PBS and 0.9 % NaCl solutions. The in vivo stability of [Al18F(2‐AMPDA‐HB)]− was assessed in healthy nude mice (n=6). Radiochemical yields between 55 % and 81 % were obtained at pH 5 and room temperature. High stability in HS was measured for [Al18F(2‐AMPDA‐HB)]−, with 90 % of F‐18 complexed after 120 min. High stability in vivo, rapid hepatobiliary and renal excretion, with low accumulation of free F‐18 in bones were measured. Thus, this new Al18F‐chelator may have a great impact on immuno‐PET radiopharmacy, by facilitating the development of new fluorine‐18‐labeled heat‐sensitive biomolecules.