Abstract 367: Imaging and diagnostic potentials of a novel cancer targeting peptide on bladder cancer in vitro and in vivo

Abstract

Abstract Background: We have previously identified a cyclic peptide PLZ4 through screening of “one bead one compound”(OBOC), that specifically binds to bladder urothelial carcinoma cells. The main objective of this study is: 1) to optimize the binding and diagnostic potential of PLZ4 on cancer cells in urine, 2) to determine the imaging potential in xenograft mouse model. Methods: PLZ4 peptide was conjugated to the fluorescent dye Alexa 488 to determine the binding affinity toward several human and canine clinical biopsy smears and paraffin-fixed bladder tumor sections. It was also tested for in vitro diagnostic efficiency with human and dog bladder cancer cell lines treated with urine for 2 and 4 hours. To determine the in vivo targeting and imaging efficacy, PLZ4 was labeled with 64Cu through the chelator DOTA or near-infrared dye DiD loaded in nanocarriers. Mice carrying subcutaneous human or dog bladder cancer xenografts generated from cell lines or clinical specimens were used for in vivo imaging. Results: Our results indicated that PLZ4-Alexa 488 bound to primary bladder cancer obtained from dog and human patients and had higher affinity in paraffin-fixed bladder tumor sections compared to H232A lung cancer xenograft tissue sections. PLZ4 also retained its affinity toward both human and dog bladder cancer cells in the presence of urine for 2 and 4 hours. Positron emission tomography (PET) imaging displayed the accumulation of PLZ4-DOTA-64Cu conjugate at human xenograft bladder cancer sites, while liver and kidney were also found to have high uptake. DiD-loaded nanomicelles decorated with PLZ4 showed a better homing property than non-targeting nanomicelles in both human and canine xenograft bladder cancers. Conclusion: PLZ4 has high imaging, diagnostic and therapeutic potential both in vitro and in vivo. It can possibly be developed for targeted delivery of radionuclides or chemotherapeutic nanoformulations in the management of bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 367. doi:1538-7445.AM2012-367