Abstract 5311: The targeting effect of radio-labeled LXY1 and LXW7 against glioblastoma on xenograft mouse model

Abstract

Abstract Glioblastoma, the most common type of primary brain tumors in adults, remains largely incurable, and surgical resection followed by radiation and chemotherapy has been shown to only slightly increase patient survival. New approaches to treat this deadly cancer are needed. Small peptide-based compounds have attracted wide interest as cancer targeting agents for the delivery of radionuclides or cytotoxic drugs to tumors. Using the “one-bead-one-compound” (OBOC) combinatorial library method, we have identified a specific ligand, LXY1, which targets the α3β1 integrin on glioblastoma cell line U87MG. We have also discovered another novel ligand containing a RGD motif, LXW7, which targets the αvβ3 integrin of U87MG cells and tumor endothelial cells. LXY1 and LXW7 demonstrated excellent tumor targeting efficacy in in vivo optical imaging studies. To further investigate the targeting property of the peptides and precisely clarify their in vivo biodistribution profile, we have conjugated LXY1 and LXW7 to the metal chelator CB-TE2A complexed with 64Cu to perform PET imaging and biodistribution studies. The results indicate 64Cu-labeled LXY1-CB-TE2A conjugate efficiently targets both orthotopic and subcutaneous glioblastoma. The LXW7-CB-TE2A conjugate also demonstrates good tumor accumulation. Both conjugates show relatively rapid clearance from tumor site and high uptake in the liver and kidney beside to tumor. The undesired high uptake of the peptides in the liver and kidney indicate both peptides in current version may be more promising in radioimaging than radiotherapy for glioblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5311. doi:10.1158/1538-7445.AM2011-5311