Abstract 4532: Fluorine-18- carboplatin derivative for imaging and therapeutic applications.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC DNA-damaging agents, such as cisplatin and other platinum drugs are the largest class of anti-cancer drugs. They are most important in the clinical use for the treatment of various cancers, although ovarian cancer cells often become resistant. Besides resistance, non-specific uptake in normal tissues and related toxicity is a dose limiting factor and affects their overall effectiveness. Knowledge of the drug concentration in the tumor as well as its overall concentration in the body of a patient will be helpful in accurately predicting the overall responsiveness of a patient to the drug. This type of knowledge can be accomplished by the development of a drug analog with positron emission tomography (PET) imaging capability, so that the accumulation of the drug in the tumor and normal organs can be tracked and quantified during the course of therapy to predict its effectiveness in a patient. Therefore, we developed a novel fluorinated carboplatin derivative, towards a hybrid agent for imaging and therapy. We synthesized 19F fluorinated carboplatin derivative using 2-(5-fluoro-pentyl)-2-methyl malonic acid by co-ordination with cis-platinum aqua complex. It was then used to treat various cell lines and compared with Cis-platin and Carboplatin at different concentrations ranging from 0.001 μM to 100 μM for 72 hrs and 96 hrs. LC50 values calculated from cell viability indicate that fluorinated carboplatin is a more potent drug than Carboplatin but less effective than Cisplatin. | Cell line | Cisplatin (μM) | Carboplatin(μM) | Fluorinated Carboplatin (μM) | |:--------- | -------------- | --------------- | ---------------------------- | ------ | | | 72 hrs | 96 hrs | 72 hrs | 96 hrs | 72 hrs | 96 hrs | | COLO 205 | 28.78 | 1.35 | >100 | 48.98 | 92.52 | 31.56 | | SK-OV-3 | 4.34 | 1.28 | 33.7 | 18.94 | 20.3 | 12.56 | | FaDu | 2.77 | <2 | 34.72 | 11.26 | 21.54 | 8.55 | | A549 | 11.01 | 3.07 | 56.56 | 31.78 | 41.18 | 24.8 | | A498 | 13.35 | 3.42 | 152.83 | 39.34 | 57.25 | 18.5 | | LNCaP | 19.2 | 7.18 | 113.51 | 63.4 | 80.09 | 46.06 | | RWPE-1 | 6.27 | <1 | 65.19 | 36.8 | 34.69 | 10.2 | | KB 3-1 | 4.13 | 2.04 | 59.82 | 26.08 | 22.76 | 13.46 | Table 1: LC50 values of fluorinated carboplatin and known platinum drugs We have also developed a microfluidic method to synthesize [18F]-2-(5-fluoro-pentyl)-2-methyl malonic acid, which will co-ordinate with cis-platinum aqua complex to yield 18F labeled carboplatin derivative. Our approach to synthesis various derivatives of 18F labeled fluorinated carboplatin will allow us to develop anticancer drugs with PET imaging capabilities. Citation Format: Gajanan K. Dewkar, Purnima Jose, Narottam Lamichhane, Celina Thadigiri, Gobalakrishnan Sundaresan, Nicholas Farrell, Jamal Zweit. Fluorine-18- carboplatin derivative for imaging and therapeutic applications. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4532. doi:10.1158/1538-7445.AM2013-4532