Abstract
1107
Objectives: Histone Deacetylase inhibitors are a class of potential drugs that can be used in the treatment of cancer. Prior study found that a serious of C-11 labeled dimethylamino benzamide analogues had high BBB penetration and the fluorosubstituted benzamide also exhibited 36 and 71 nM inhibitory activity against recombinant human HDAC1 and HDAC2, respectively .Thus, the F18-labeling benzamide might be a potential PET imaging probe for histone deacetylase expression. Here, a novel F-18 labeled dimethylamino benzamide derivative 18F-MH01 was prepared via the copper mediated radiofluorination and evaluated as imaging probe for HDAC expression in brain cancer in vivo
Methods: The F-18 labeled dimethylamino benzamide 18F-MH01 was obtained via copper mediated radiofluorination and purified by HPLC successfully. Two tumor cell lines U87MG and GBM8401 were applied for in vitro and in vivo study. Result: The radiochemical yield of F-18 MH01 is about 15 ± 3.3% and radiochemical purity ≧ 95%. The cellular uptake studies showed 18F-MH01 had higher uptake in U87-MG cell line than in GBM8401 cell line and the significant uptake of this tracer is 11.92 ± 0.37% in U87MG cell line (105cell) after two hours incubation. The biodistribution showed that the F-18 MH01 possess higher T/M and T/B ratio in U87MG bearing mice (2.60 ± 0.20 and 3.04 ± 0.49 ) than the GBM8401 bearing mice (1.95 ± 0.63 and 1.64 ± 0.63 ) after two hours injection. The micro PET imaging studies also showed the higher accumalation in bearing U87-MG model compared with the GBM8401 bearing mice for this tracer. Conclusions: The F-18 MH01 can be prepared rapid and efficient via two-step copper mediated radiofluorination and the biological evaluations indicate that F-18 MH01 might be a potential PET tracer for HDAC expression in U87MG brain cancer.