Lisa Russelli, Jonathan Martinelli, Francesco De Rose, Sybille Reder, Michaels Herz, Markus Schwaiger, Wolfgang A. Weber, Lorenzo Tei, C. D’Alessandria. (16-12-2019).

ChemMedChem, 2019

Department: 

Research Area C

Abstract: 

Positron emission tomography (PET) is a non-invasive molecular imaging technology 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 leads 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 have been 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 in different 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 240min in human serum (HS), EDTA 5mM, PBS and 0.9% NaCl solutions. In vivo stability of [Al18F(2- AMPDA-HB)]-  was assessed in healthy nude mice (n=6). RCYs between 55% and 81% were obtained at pH 5 and rt. High stability in HS was measured for [Al18F(2-AMPDA-HB)]- , with 90% of F-18 complexed after 120min. High stability in vivo, a fast hepatobiliary and renal excretion, with irrelevant accumulation of free F-18 in the bones were measured. Thus, this new Al18F-chelator may have a great impact on immunoPET radiopharmacy, by facilitating tdevelopment of new fluorine-18 labeled heat-sensitive biomolecules.