Synthesis and evaluation of F-18-INER-1577 as HDACi Imaging Agent in Mice

Objectives: Histone deacetylases (HDACs) are considered viable drug targets for therapeutic applications including cancer and neurological disorders. Methods: In the present paper, the synthesis of 18F-labeled INER-1577-3 (a HDAC inhibitor which has shown in vitro and in vivo activity in HDAC1,2,3,6,8 protein and SAMR1/SAMP/8 rodent animal model) is described for the first time. The radio synthesis has been approached by reaction of the non-radioactive precursor N-(4-amino-[1,1'-biphenyl]-3-yl)-4-((dimethylamino)methyl)benzamide with [18F] flouride in basic media. Results: Despite the presence of more than one reactive site in the chemical structure of the precursor, acceptable radiochemical yield (3%, decay corrected to the end of bombardment), specific activity ( 100±25 μCi/ 100μL ) and radio chemical purity values (95%) were obtained in reasonably short preparation times(40 min). Conclusion: Despite the moderate radio chemical yield, final radioactivity and radioactivity concentration values (1.870.3GBq and 180MBq/ml, respectively) should be sufficient for putative in vivo studies in animals.