This Small Business Technology Transfer Phase I project takes an innovative approach at tumor targeting by investigating an entirely novel tumor targeting platform that utilizes bone marrow derived, circulating tumor homing cells as natural vectors. Through screening of phage display peptide libraries we have identified high affinity peptide ligands that bind these cells with high specificity. These high affinity, high specificity peptide ligands and their applications for molecular imaging of tumor?s blood supply represent the innovation in this Phase I project. Radiolabeled peptide directed compounds will be synthersized and their potential to deliver molecular ?payloads? specifically to malignant vasculature in a mouse model of cancer will be characterized. The results from this development effort will provide proof-of-principle validation for a new targeting paradigm in which circulating tumor localizing cell populations can be exploited for highly transformative and innovative technology development for the benefit of cancer patients.
The broader impact of this project and the commercialization of the molecular diagnostic tracer developed here will have important implications for furthering oncology care through personalized approaches: First, specific and sensitive imaging based on monitoring of homing of circulating cells to tumor tissue will be beneficial for tumor staging and re-staging. Second, in addition the outcomes of this development effort would provide more predictable information relevant to treatment that has been lacking so far. Close assessment of patient?s response to treatment by monitoring the presence or absence of circulating tumor homing cells would improve treatment outcomes and guide the development of personalized therapies. Third, especially promising clinical direction is to selectively deliver anti-angiogenic, and therapeutic compounds as anticancer strategies. Because endogenous cells are utilized as natural biologic vectors, the barriers to commercialization and clinical implementation of our innovative diagnostic tracer are much lower than for other emerging technologies.
In treating cancers, many lives could be saved and treatments improved if we could detect cancers earlier and track their responses to treatment accurately. The oncology community has numerous imaging tools all capable of viewing gross anatomical features but less sensitive to quantifying cancer molecular signatures such as the presence of functional components that drive cancer progression and metastasis. There is a need for enhanced medical imaging agents that can enable noninvasive analysis of specific biological processes within cancerous tissues. Enhanced tools are needed that can increase sensitivity, specificity, and level of quantification of tumor progression for purposes of staging, developing treatment plans, and evaluating responses to therapy. Clavé Biodesign addresses this unmet clinical need by developing a novel approach using circulating, tumor homing cells as natural mechanism (or vector) to target nuclear imaging agents directly to tumor’s blood supply with high degree of sensitivity and selectivity. The objectives of this project were to prepare imaging agents for use with positron emission tomography scanners and to investigate their properties in a mouse model of cancer using a variety of characterization methods. We successfully synthesized the proposed chemical entities and confirmed the chemical identity of each compound by mass spectrometry. Further, we studies by imaging procedures the uptake and biodistribution of the new tracers in tumor bearing mice. The standardized values for tumor uptake and tumor-to-normal tissue ratios determined by quantitative image analysis were utilized in a mathematic model to calculate adsorbed doses. We identified the tracers with the most favorable absorbed dose safety profiles and demonstrated their potential to be clinically useful as tumor imaging biomarkers. In summary, we have successfully and thoroughly completed the objectives of our Phase I proposal. These studies demonstrate the feasibility of our imaging approach and warrant further research and development efforts to move the most promising agents toward clinical application.
