Molecular Imaging of Ovarian Carcinoma Angiogenesis

This purpose of this proposal is to use high resolution microPET technology to image ovarian cancer integrin expression in vivo. Ovarian cancer is angiogenesis dependent. Integrin av 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 av 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 av Beta 3 affinityspecificity 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 subjected to GLP toxicity study. Exploratory IND eIND application is currently underway and first-in-human studies are being planned. Further test of the optimal radiotracer in different ovarian cancer models to correlate the tracer uptake with tumor integrin expression is currently underway as a non-cost of extension Aim 2.