Molecular, cancer-specific, intraoperative imaging of breast surgical margin Tumor margin determination is critical for breast conserving surgery. Current re-excision rates range from 20% to 30%. Intraoperative tumor margin determination would enable complete tumor removal during the first surgery while the patient is still on the operating table. Currently, there is no method that is molecularly and cancer-specific, and can be used in the operating room to help surgeons assess breast cancer surgical margins to eliminate re-excision. The ultimate goal of this project is to develop a molecular, cancer-specific, imaging tool that is rapid and low-cost and do not require a pathologist?s review under a microscope to help surgeons assess if the surgical margin is clean in the operating room to reduce the re-excision rate. Together with Drexel University, AQD Life Sciences (AQDLS) has created a cancer-specific molecular probe consisting of patented near infrared (NIR) CdPbS aqueous quantum dots (AQDs) conjugated to anti-Tn antigen antibody (Ab). Tn is a proven cancer- specific glycan marker on epithelial cancer cells. With virtually no interference from tissue autofluorescence, the NIR Tn-AQDs probe exhibited 95% sensitivity and 96% specificity in differentiating breast cancer (BC) from normal tissues and benign breast conditions (BBC) in tissue arrays from 395 tissue blocks from 115 patients. Data on 12 cases using an animal imaging facility, IVIS imaging system (PerkinElmer) indicate the NIR Tn- AQDs molecular probe can differentiate positive margins from negative margins. However, the small-animal imaging system is expensive. Further data on 1 case showed that high-quality margin imaging can be obtained using a preliminary setup of LED light sources, excitation filters, dichroic mirrors, emission filter, and an NIR camera on a breadboard on a bench. With this success, the immediate goal of this Phase-I application is to develop a prototype NIR imaging system specifically tailored to the optical characteristics of the cancer- specific, NIR Tn-AQDs molecular probe and test it on 40 patients for sensitive and specific surgical margin imaging over the one year period. All patients presenting for breast conserving surgery with a diagnosis of Ductal Carcinoma in Situ or invasive breast cancer (lobular or ductal) are eligible. The proposed development of a reliable imaging system tailored specifically to the NIR Tn-AQD molecular probe will lead to a quantitative cancer-specific margin imaging tool that will eventually reduce re-excision rate to <6%.
Breast conservation surgery has a re-excision rate of 20%-30%. This study seeks to eventually reduce the re- excision rate by developing a novel surgical margin imaging tool using a cancer-specific near-infrared molecular probe and the development of the imaging system specifically tailored to the characteristics of the molecular probe for optimal sensitivity and specificity.
