Friday, April 19, 2024
4/19/2024
Most patients with melanoma die from metastatic disease as the result of circulating tumor cells (CTCs) spreading from a primary tumor through the blood to vital organs. Despite significant progress in the development of in vitro CTC-detection assays, they still have low sensitivity due to the small samples of blood taken. To overcome these problems, we developed in vivo photoacoustic (PA) flow cytometry (PAFC) and demonstrated its feasibility in pilot trials with melanoma patients where we used melanin in CTCs as an intrinsic PA contrast agent. These trials identified the key limitations of the PAFC platform, such as a stationary laboratory setup with a large expensive laser, a motion- and skin-pigmentation-sensitive recording system, no spectral identification of melanoma CTCs in the blood background, a detection limit 20–30-fold lower than the ultimate threshold, and limited clinical data. These obstacles prevent the routine use of this promising technology. The goal of our Phase I STTR proposal is to demonstrate the feasibility and clinical relevance of an advanced PAFC-based “Cytophone” prototype for early, fast (from 20 sec to a few min), noninvasive (no blood draw), label-free (no exogenous contrast agents), and safe (no skin photodamage or blood contamination concern) detection of CTCs in melanoma patients. To achieve this goal, we will optimize the Cytophone’s parameters and eventually explore its clinical capabilities during testing of melanoma patients. We expect to obtain statistically significant data that will demonstrate an unprecedented 1000-fold increase in sensitivity, allowing us to detect 1 CTC in 1 liter of blood with our robust, wearable, and portable Cytophone device. This level of sensitivity will allow us to detect CTCs released from small tumors (e.g., = 1 mm), which are often not identified with current diagnostic techniques. The goal of our Phase II STTR proposal is to develop commercial Cytophone prototypes to be tested in multicenter clinical trials. We expect that the Cytophone can eventually be used in melanoma-focused clinics throughout the world for early diagnosis, monitoring treatment efficiency, and as a mass melanoma screening tool (as the mammogram is used for breast cancer).
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
