Department of Chemistry, University of Warwick, Coventry CV4 7AL, U.K.
School of Pharmacy, Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT, U.K.
Inorg Chem. 2023 Dec 18;62(50):20745-20753. doi: 10.1021/acs.inorgchem.3c02245. Epub 2023 Aug 29.
A novel photoactivatable Pt(IV) diazido anticancer agent, , bearing a pendant deferoxamine (DFO) siderophore for radiometal chelation, has been synthesized for the study of its behavior with radionuclide imaging. complexation of Fe(III) and Ga(III) ions yielded new heterobimetallic complexes that maintain the photoactivation properties and photocytotoxicity of the parent Pt complex in human cancer cell lines. Radiolabeled ( = 68 min, positron emitter) was readily prepared under mild conditions and was stable in the dark upon incubation with human serum. PET imaging of in healthy mice revealed a promising biodistribution profile with rapid renal excretion and limited organ accumulation, implying that little off-target uptake is expected for this class of agents. Overall, this research provides the first imaging study of the whole-body distribution of a photoactivatable Pt(IV) azido anticancer complex and illustrates the potential of radionuclide imaging as a tool for the preclinical development of novel light-activated agents.
一种新型光活化的 Pt(IV)叠氮抗癌试剂 ，带有一个悬挂的去铁胺 (DFO) 铁载体用于放射性金属螯合，已被合成用于研究其与放射性核素成像的 行为。Fe(III)和 Ga(III)离子的配合物生成了新的异双金属配合物，在人癌细胞系中保持了母体 Pt 配合物的光活化特性和光细胞毒性。在温和条件下很容易制备放射性标记的 （ = 68 min，正电子发射体），并在黑暗中与人血清孵育时稳定。在健康小鼠中进行的 PET 成像显示出有希望的生物分布特征，具有快速的肾脏排泄和有限的器官积累，这意味着此类药物不太可能出现脱靶摄取。总的来说，这项研究首次对光活化的 Pt(IV)叠氮抗癌复合物的全身分布进行了 成像研究，并说明了放射性核素成像作为新型光激活试剂临床前开发工具的潜力。
