Molecular Imaging of Ovarian Carcinoma Angiogenesis.

摘要

This purpose of this proposal is to use high resolution microPET technology to image ovarian cancer integrin alpha v beta 3 expression in vivo. Ovarian cancer is angiogenesis dependent. Integrin alpha v beta 3, a key player in tumor angiogenesis and metastasis, has been identified as a target for diagnostic and therapeutic interventions for several highly proliferative and metastatic tumor types. Specific Aim 1: To develop and optimize 18F-labeled RGD peptides for ovarian carcinoma targeting. Specific Aim 2: To test 18F-RGD peptide tracers in ovarian carcinoma models of different tumor integrin alpha v beta 3 expression levels in order to correlate the magnitude of tumor uptake with receptor density. Major Findings: In year 1, we have synthesized a series of multimeric RGD peptides with high integrin alpha v beta 3 affinity/specificity and labeled these peptides with F-18 for PET imaging of integrin expression in vivo (Aim 1). In year 2, we have also established several ovarian cancer models with differentiated integrin levels (Aim 2). One of the dimeric RGD peptide tracer 18F-FPRGD2 with high tumor targeting efficacy and favorable in vivo kinetics has been identified as the lead compound for future translational work.