BETA CAMERA AND LAPAROSCOPIC PROBE FOR SURGICAL CANCER REMOVAL. - DESCRIPTION (provided by applicant): The recent development of the Solid State Photo-Multiplier (SSPM) has created an unprecedented opportunity to develop a safe, highly sensitive and compact beta camera for use during cancer surgery, and a Laparoscopic beta probe for intra-abdominal cancer detection. We will build these devices, incorporate them into our marketed intra-operative control unit, test them with phantoms and pursue safety certifications for their eventual use in clinical trials during the Phase II. Significance: Surgery is the only certain cure for cancer; however, its curative ability is compromised by the potential of leaving behind microscopic traces of the tumor, known as margins. In breast cancer, for example, there is a 20% recurrence rate after breast-conserving surgery (lumpectomy) due to missed margins. A beta camera capable of surveying the tumor bed, intraoperatively, and imaging visually undetectable, minute amounts of cancer cells, could significantly reduce recurrence rate of many cancers such as melanoma, breast and prostate, and increase survival. In addition, it may enable more breast cancer patients to become candidates for breast saving lumpectomies and improve the psychological recovery from breast cancer. A Laparoscopic beta probe would give a new "vision" to the surgeon and facilitate detection and complete removal of abdominal cancer in a minimally invasive manner. Background: F-18 atoms emit positrons (beta rays) that in turn generate gamma rays. Gamma rays travel tens of cm in tissue, while beta rays have a range of~2mm. Beta emitting isotopes are ideal for intraoperative imaging since background radiation would not interfere with identification of margins. Until now, beta cameras have suffered from one of two serious flaws that prevent their use in cancer surgery 1. The thin shielding required for positron detection provides insufficient insulation from the high voltage photomultiplier tubes (PMTs), or 2. The long fiber-optic coupling used to separate the high voltage from the patient greatly reduces sensitivity. Preliminary Data: We have previously developed a beta camera with the resolution and sensitivity to detect minute (5 mg) cancer deposits. Over the last year we have tested various configurations of SSPMs and scintillators; our research shows that SSPMs have higher sensitivity than photomultiplier tubes while operating at ~ 50 volts. They are also very small (1x1 mm). We conducted preliminary testing, in which we measured an absolute efficiency of 15% for a small plastic scintillator directly coupled to an SSPM, as opposed to 0.2% for an identical scintillator coupled fiber-optically to a PMT. We have built a prototype of the SSPM based beta camera in an small scale and demonstrated its feasibility. Research and Development Plan: We will build the camera with a sheet of red plastic scintillator and a 2 dimensional array of SSPMs. We will also build a dual detector beta probe in a 5 mm diameter for laparoscopy using SSPMs and plastic scintillators. We will then study the effect of temperature variance from 25 to 37 oC, and investigate various methods to compensate for temperature dependence. Once these issues have been addressed we will optimize the sensitivity of the camera, and perform characterization experiments. During the design process we will implement all applicable electrical and biological safety standards. Then we will determine limits of tumor detection of this camera with realistic phantoms. In Phase II we will conduct trials with our long-time collaborators at the John Wayne Cancer Institute on melanoma and breast cancer patients, at Cornell on prostate cancer, and at Memorial Sloan Kettering in abdominal Laparoscopic cancer detection.
