Molecular Imaging of Ovarian Carcinoma Angiogenesis; Annual rept. 1 Feb 2006-31 Jan 2007

摘要

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 , 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. The interaction between vitronectin and integrin is essential for ovarian cancer cell survival and invasion. The integrin expression has been identified as a marker of poor prognosis in advanced-stage ovarian cancer. Its role in ovarian cancer development and as treatment target is under-developed. 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 &(number sign)945;v&(number sign)946;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 alphavbeta3 affinity/specificity and labeled these peptides with F-18 for PET imaging of integrin expression in vivo (Aim 1). We have also established several ovarian cancer models with differentiated integrin levels (Aim 2). Further test of the optimal radiotracer in different ovarian cancer models to correlate the tracer uptake with tumor integrin expression is currently underway (Aim 2).