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

Positron emission tomography (PET) is a non\u2010invasive molecular imaging technology that is constantly expanding, with a high demand for specific antibody\u2010derived imaging probes. The use of tracers based on temperature\u2010sensitive molecules (i.\u2009e. Fab, svFab, nanobodies) is increasing and has led us to design a class of chelators based on the structure of 2\u2010aminomethylpiperidine (AMP) with acetic and/or hydroxybenzyl pendant arms (2\u2010AMPTA, NHB\u20102\u2010AMPDA, and 2\u2010AMPDA\u2010HB), which were investigated as such for {Al18F}2+\u2010core chelation efficiency. All the compounds were characterized by HPLC\u2010MS analysis and NMR spectroscopy. The AlF\u201018 labeling reactions were performed under various conditions (pH/temperature), and the radiolabeled chelates were purified and characterized by radio\u2010TLC and radio\u2010HPLC. The stability of labeled chelates was investigated up to 240\u2005min in human serum (HS), EDTA 5\u2005mM, PBS and 0.9\u2009% NaCl solutions. The in\u2005vivo stability of [Al18F(2\u2010AMPDA\u2010HB)] 12 was assessed in healthy nude mice (n=6). Radiochemical yields between 55\u2009% and 81\u2009% were obtained at pH\u20055 and room temperature. High stability in HS was measured for [Al18F(2\u2010AMPDA\u2010HB)] 12, with 90\u2009% of F\u201018 complexed after 120\u2005min. High stability in\u2005vivo, rapid hepatobiliary and renal excretion, with low accumulation of free F\u201018 in bones were measured. Thus, this new Al18F\u2010chelator may have a great impact on immuno\u2010PET radiopharmacy, by facilitating the development of new fluorine\u201018\u2010labeled heat\u2010sensitive biomolecules