Abstract 2433: Comparisons between an IRDye 800CW-labeled PSMA-targeted small molecule and antibody for preclinical small animal imaging

Abstract

Abstract Prostate cancer continues to be the second leading cause of cancer death in men in 2011. Deciphering the progression and mechanisms contributing to the metastatic spread of this disease is critical to our overall understanding of how to approach treatment and/or therapy. Prostate-specific membrane antigen (PSMA) is a possible therapeutic target for the disease and is the focus of several cancer therapies currently in clinical trials. Near infrared (NIR) fluorescence imaging for cancer diagnosis and treatment is gaining attention for preclinical as well as clinical applications. IRDye 800CW is a NIR fluorophore exhibiting superior target-to-background ratios when conjugated to targeting moieties such as antibodies, peptides, and small molecules. Here we assess two different PSMA-targeted compounds conjugated to IRDye 800CW: the small molecule YC-27 and a PSMA-specific antibody. In vitro binding kinetics for both compounds exhibit expected dose dependent increases with increasing concentrations. Both compounds were successfully blocked with their unlabeled counterpart; however, neither blocked the other suggesting different PSMA epitopes. Although direct comparisons are inappropriate due to differences in molecular structures and labeling density, assessment of their respective pharmacokinetics is possible. Microscopy of prostate tumor cells incubated with each probe revealed a slower internalization of the small molecule when compared to the internalization of the antibody. Specificity of the labeled compounds in vivo was determined in male athymic nu/nu mice implanted with 22Rv1 (PSMA positive) or PC3M-LN4 (PSMA negative) prostate cancer cells (106). Mice received either IRDye 800CW YC27 (1 nmole) or IRDye 800CW PSMA (50 µg) followed by non-invasive fluorescent optical imaging of 800nm signals on the Pearl Impulse Small Animal Imager. At the study endpoint, organs and tumors were excised and imaged to assess residual probe localization. In vivo clearance patterns for these labeled molecules differed with the YC27 clearing via the kidneys and the antibody clearing through the liver. These subtle differences between the two imaging agents provide valuable options to investigators with specific requirements in their animal research. 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 2433. doi:1538-7445.AM2012-2433