Tumor imaging by using a combination of positron labeled EGFR tyrosine kinase inhibitors and stealth nanocarriers

733 Objectives: PET with epidermal growth factor receptor (EGFR) kinase-specific radiolabeled tracers could provide the means for imaging of EGFR expression and signaling activity in tumors in patients during therapy with EGFR inhibitors. Our group has develop PET tracers irreversibly binding to EGFR, However because of significant hepatobiliary clearance and intestinal reuptake of the morpholino-[124I]-IPQA (SKI212243) and overall hydrophobicity with octanol water coeeficients of up to 4, additional formulation steps are needed for optimization of the pharmacokinetics of these imaging agents. Thus these drugs are interesting candidates for utilizing lipid base nanoparticles, which improve the solubility of the drugs but also increase the circulation time in the blood stream and spontaneously target to the tumors. In our work we compared the combined targeting approach by using EGFR kinase targeting SKI212243 (SKI243) embedded in liposomes and bare SKI243 as a PET tracer. Methods: EGFR inhibitors were encapsulated in to PC/chol/PEG-PE liposomes of 100nm. PET imaging of Nude mice bearing A431 and H3255 was done in 0.25, 1, 2, 24, 48, 72 h time points by using MicroPET. Biodistribution of the SKI243 was measured with imaging agent and liposomal imaging agent. Results: SKI243 and liposomal SKI243 are taken up to the tumor. Liposomal drug stays longer in the blood and consequently increase the tumor uptake. We found that uptake in tumor could be increased 3-6 fold with the use of liposomal nanocarriers, although liver and lungs also show some increased uptake. Conclusions: Liposomal formulation of SKI243 appears promising to enhances the in vivo efficiency in tumor imaging by significantly increasing the targeting of lipophilic tyrosine kinase inhibitor drugs.