Fast-Track proposals will be accepted. Direct-to-Phase II proposals will be accepted. Number of Anticipated Awards: 3-5 Budget (total cost, per award): Phase I: up to $400,000 for 12 months Phase II: up to $2,000,000 for 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Page 95 Summary The purpose of this technology-agnostic contract solicitation is to bring highly sensitive cancer-specific imaging agents and technologies capable of detecting very small volume (1 mm3 ) tumors in humans to clinical utility. Current imaging technologies/techniques are in use for non-invasive cancer detection, but clinical methods are limited to detecting masses several millimeters to centimeters in size. To image small primary or metastatic tumor sites composed of 1 – 10 million cells, imaging sensitivity must be improved. This can be achieved without significant hardware advances by improving the contrast between diseased and healthy tissue captured in the image. Thus, there is a clinical need for techniques that improve image contrast between tumors and surrounding normal tissue. There are several methods that rely on the use of specialized agents that are activated when coupled to a tumor target. Such activatable agents dramatically increase the contrast between small tumor cell masses and surrounding tissue. Efforts to develop activated imaging agents and techniques have been ongoing for over a decade, and successful demonstration in cancer-bearing animals has been achieved. These developmental successes now need to be translated for clinical use. This SBIR solicitation thus supports translation of novel activatable agents and/or techniques for sensitive cancer detection in human subjects. Clinical translation and validation should be the primary goals of the proposed research. The bulk of the proposed research must focus on translating improvements in imaging sensitivity to a clinical environment with the goal of demonstrating that tumor cell aggregates on the order of 1 mm3 in volume can be detected in cancer patients. Research toward development and establishing biological safety of the agent or technique in preparation for clinical validation will be accepted under this solicitation in Phase I. Thus, this solicitation supports translation of developing technologies for small tumor detection in human subjects. It is not intended to support continued major development and testing of techniques or novel agents. Any technique or strategy that dramatically enhances contrast between very small cancer and normal tissue is acceptable for consideration, which can include software techniques (such as AI/ML) that have already been validated in cancer-bearing animal models prior to submission of the application.