Facile Synthesis of a Pt(IV) Prodrug of Cisplatin and Its Intrinsically Pt Labeled Analog: A Step Closer to Cancer Theranostic.

Background Aims And Objectives: Cisplatin is extensively used in chemotherapy for treatment of a broad range of cancers. But its undesired side reactions with biomolecules that lead to severe side effects especially on kidney and nervous system, are limiting its clinical utility. To reduce its side effects, the kinetically inert Pt(IV) prodrug was recognized as an alternative approach from satisfactory results of preliminary experiments. But, its approval as anticancer drug for clinical use requires detailed investigations of its anticancer action and pharmacological pathways by employing its analogue which can be traced by a suitable technique. As a step closer towards translation of Pt(IV)-based prodrug from research to clinical level, a protocol for efficient synthesis of Pt-radiolabeled Pt(IV) prodrug was devised.

Materials And Methods: In order to achieve the aim, we started synthesis from elemental platinum avoiding lengthy steps. The synthesis protocol was standardized on its cold analogue, as [PtCl(NH)(OCOCHCHCOOH)] which has been characterized with nuclear magnetic resonance (H, C{1H} and Pt{1H}) spectroscopy, microanalyses and cyclic voltammetry. Also, cytotoxicity of [PtCl(OCOCHCHCOOH)(NH)] was evaluated against MCF-7 human breast cancer cell lines using cisplatin as test control.

Results: Intrinsically, Pt-labeled analogue of prodrug was obtained with high radionuclidic and radiochemical purity. It was confirmed by chromatography and γ-ray spectrometry.

Conclusion: The Pt-radiolabeled prodrug was synthesized in a facile manner. It can be utilized in evaluating the mechanism of anticancer action and pharmacokinetics by enabling synergistic use of molecular imaging and targeted drug delivery.