Zhou Dong, Chu Wenhua, Xu Jinbin, Jones Lynne A, Peng Xin, Li Shihong, Chen Delphine L, Mach Robert H
Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
Department of Radiology, School of Medicine, Washington University in Saint Louis, St. Louis, MO 63110, USA.
Bioorg Med Chem. 2014 Mar 1;22(5):1700-7. doi: 10.1016/j.bmc.2014.01.019. Epub 2014 Jan 24.
Imaging of poly (ADP-ribose) polymerase-1 (PARP-1) expression in vivo is a potentially powerful tool for developing PARP-1 inhibitors for drug discovery and patient care. We have synthesized several derivatives of benzimidazole carboxamide as PARP-1 inhibitors, which can be (18)F-labeled easily for positron emission tomographic (PET) imaging. Of the compounds synthesized, 12 had the highest inhibition potency for PARP-1 (IC50=6.3 nM). [(18)F]12 was synthesized under conventional conditions in high specific activity with 40-50% decay-corrected yield. MicroPET studies using [(18)F]12 in MDA-MB-436 tumor-bearing mice demonstrated accumulation of [(18)F]12 in the tumor that was blocked by olaparib, suggesting that the uptake of [(18)F]12 in the tumor is specific to PARP-1 expression.
体内聚（ADP - 核糖）聚合酶 -1（PARP -1）表达成像对于开发用于药物发现和患者护理的PARP -1抑制剂而言是一种潜在的强大工具。我们已经合成了几种苯并咪唑甲酰胺衍生物作为PARP -1抑制剂，它们可以很容易地用（18）F标记用于正电子发射断层扫描（PET）成像。在所合成的化合物中，12种对PARP -1具有最高的抑制效力（IC50 = 6.3 nM）。[（18）F]12是在常规条件下以高比活度合成的，衰变校正产率为40 - 50％。在携带MDA - MB - 436肿瘤的小鼠中使用[（18）F]12进行的微型PET研究表明，[（18）F]12在肿瘤中的积聚被奥拉帕尼阻断，这表明[（18）F]12在肿瘤中的摄取对PARP -1表达具有特异性。
