Project Summary Every year, approximately 100,000 men in the US will undergo radical prostatectomy as a surgical treatment for prostate cancer. Radical prostatectomy is highly effective but frequently severs the patient's neurovascular bundle, compromising his fertility, urinary continence, and/or erectile function. The neurovascular bundle is often severed during radical prostatectomy because surgeons have no way to detect cancer involvement of the bundle during surgery. Providing surgeons with an accurate tool to detect prostate cancer intraoperatively could enable them to increase the use of nerve-sparing procedures. Radioguided surgery with 99mTc-PSMA holds significant promise for detecting cancer during surgery. However, the technique has poor, centimeter-scale spatial resolution. In this project we are proposing a novel technology called electron radioguided surgery (eRGS) that dramatically boosts the sensitivity of conventional radioguided surgery. The approach measures the electrons emitted instead of the gamma particles emitted by conventional 99mTc radiopharmaceuticals. The measurement is made possible by direct detection of electrons in a solid-state CMOS sensor. The sensor is incorporated into a probe suitable for manual, laparoscopic, and robotic laparoscopic surgery. This project will optimize and test the electron detecting method in vitro and in vivo before proceeding to controlled product development. If successful, electron radioguided surgery could reduce the complications and morbidity associated with the current surgical treatment of prostate cancer.