Development of a Novel Peptide Platform for Targeted PET Imaging and Radiotherapy of Breast Cancer

项目总结/文摘

Project Summary/Abstract The PI is committed to the development of novel tools for the diagnosis and treatment of breast cancer, with a short-term objective to gain impactful and necessary training and a long-term commitment towards a career path in breast cancer radiology and oncology. The PI recently joined the community of dedicated cancer researchers at Memorial Sloan Kettering Cancer Center (MSK) as a postdoctoral research scholar in the Lab of Professor Jason S. Lewis, an internationally renowned expert in PET probe development and translational science. The Advising Committee, comprised of a Primary Mentor (Lewis) and Co-Mentors (Drs. Weber and Morris) and PI have identified specific areas in cancer biology, pathophysiology, and radiology which the PI will need to further develop to establish himself as an independent researcher; they have cooperatively formulated a plan for training and development. The proposed F32 training plan outlines a set of career development activities and workshops—including grant writing, public speaking, lab management, and mentoring students— designed to enhance the PI’s ability to be an independent investigator. The PI’s choice of sponsors, research project, and training will provide a solid foundation to reach his present and future academic and professional goals (please see Biosketches and Facilities & Resources). Breast cancer remains the most common cancer among women in the United States, with approximately 12% of women developing breast cancer over the course of her lifetime. 10-20% of this patient population is affected by triple-negative breast cancer (TNBC), a subtype with particularly poor prognosis in part due to the lack of effective targeted therapies. The Lewis Lab has developed a pH(low) insertion peptide (pHLIP®), which targets tissues with increased extracellular acidity—a hallmark of virtually all cancerous tissue—through cellular membrane insertion. Affinity of pHLIP® for this universally exhibited tumoral trait highlights its potential for use in oncologic clinical applications, and in particular for TNBC, as pHLIP® targeting is unaffected by the absence of ER, PR, and HER2 characterized by TNBC. Therefore, the objective of this project is multifaceted: a) to optimize pHLIP® for use as a general diagnostic tool with generator-produced radiometals in an effort to decouple clinics from the need for a neighboring cyclotron, b) to extend the clinical applications of pHLIP® to targeted therapy and theranostics for TNBC, c) to develop a novel 225Ac-based pHLIP® radiobioconjugate for targeted α-therapy of TNBC, and finally, d) to make a lasting contribution to patient care through the development of a motivated, independent investigator committed to the conquest of cancer.