A targeted peptide for PET imaging of cancer

DESCRIPTION (provided by applicant): ATN-161 (Ac-PHSCN-NH2) is a five amino acid peptide with potent anti-tumor, anti-angiogenic and anti-metastatic activity that specifically localizes to tumor cells and tumor endothelium. ATN-1 61 binds to several fully activated integrins which are involved in angiogenesis, metastasis and tumor growth and are present in both tumor and angiogenic endothelial cells. A Phase I trial evaluating the safety of ATN-1 61 in advanced cancer patients is currently ongoing at Fox Chase Cancer Center. The objective of this fast-track STTR proposal is to develop a novel, targeted PET imaging agent derived from the sequence of ATN-161. The potential utility of receptor-targeted imaging methods for oncology is substantial and represents an advance from less specific probes. The current market for radiopharmaceutical imaging agents is estimated to be $ 1.8 8. We have recently demonstrated the ability of a derivative of ATN-1 6lto specifically localize to tumor vasculature in tumor bearing mice, suggesting the possible utility of this approach for imaging. The ATN-161 derivative used in that study was detected in the tumor vasculature up to 24 hours post injection, suggesting that despite its fast clearance from plasma (tl/2-24 mm.), the interaction of ATN-161 with its target appears to belong-lived. Thus, derivatives of ATN-161 may possess many of the desired properties for an ideal PET imaging agent for oncology: high affinity and specificity, accessibility to target, utility in a broad spectrum of tumor types, small size and rapid clearance from the plasma. The objective of the Phase I portion of this grant application is to identify a candidate ATN-181 peptide derivative from a series of already synthesized analogs to be used for proof of principle PET studies. If proof-of-principle can be demonstrated, the candidate identified in Phase I will be advanced into pre-clinical development in the Phase II portion of this application, which would culminate with the filing of an IND to advance the candidate into Phase I clinical trials.