A novel design of integrin α2β1 targeting peptide probe for molecular imaging in prostate cancer

UnrestrictedProstate cancer is one of the leading causes of cancer-related deaths in the United States and Europe. Despite the fact that prostate-specific antigen (PSA) screening has greatly increased the number of patients with early stage prostate cancer who can be cured by radical prostatectomy, about 40% of prostate cancers are first detected at an advanced stage and half of these are found to be extracapsular at pathologic staging. Therefore, development of an accurate noninvasive imaging technique to detect primary, recurrent and residual prostate cancer is critical for the effective management of this group of patients.; Accumulating experimental evidence indicates that integrins presented on various tumor types are differentially expressed during tumor transformation, progression, and metastasis. Development of integrin cell expression profiles of individual tumors may have further potential in identifying a cell surface signature for a specific tumor type and/or stage. Multiple lines of literature studies indicated that the upregulation or overexpression of α2β1 integrin may correlate with tumor progression in human prostate cancer. For example, the more aggressive PC-3 cell line has the highest expression of α2β1 integrin compared with other less aggressive cell lines, such as CWR-22 (medium expression of α2β1) and LNCap (low expression of α2β1). Noninvasive imaging of this receptor with radiolabeled peptides that specifically target α2β1 integrin could therefore be useful to decipher the invasive potential of prostate cancers.; High sensitivity positron emission tomography coupled with computed tomography for anatomical evaluation, PET/CT, has become a critical diagnostic imaging tool in the identification of a diverse group of malignancies. In this study, we use the knowledge of chemistry, radiochemistry, biochemistry, biology and molecular imaging to develop clinically translatable α2β1 integrin targeting PET probes for prostate cancer imaging. A series of α2β1 integrin targeting peptides were synthesized and their specificity was verified both in vitro and in vivo at the molecular level in preclinical prostate tumor models. The success of the proposed study may provide a better understanding of basic biological mechanisms of prostate cancer, help us more appropriately select patients considered for anti-integrin α2β1 treatment, and allow the evaluation of disease course and therapeutic efficacy at the earliest stages of treatment