Cerenkov Multi-Spectral Imaging (CMSI) for Adaptation and Real-Time Imaging in Radiotherapy

PROJECT SUMMARY Understanding of tumor molecular characteristics during a course of radiotherapy (RT) treatment is crucial to assess the efficacy of the treatment and adapt radiation dosage to optimize outcomes. Unfortunately, this cannot be routinely achieved by current diagnostic nuclear imaging modalities due to complex logistics and prohibitive costs. Alternatively, Cerenkov Emission (CE) is an optical phenomenon that accompanies external beam radiation from a linear accelerator and has been demonstrated for in vivo dosimetry and spectroscopy during radiotherapy. This approach shows great potential, but the low photon response from commercially available detectors has limited its impact in clinical radiotherapy practice. The recent development of highly sensitive, compact silicon photomultiplier (SiPM) devices enables arrays of CE detectors to be customized in any shape and placed directly on a patient’s body to provide a much enhanced signal, thus enabling CE to become a new, routine clinical tool for daily molecular tumor characterization during radiation treatment. This Phase I STTR will assess the feasibility of this revolutionary Cerenkov Multi-Spectral Imaging (CMSI) innovation, which is the product of collaboration between researchers in the Radiation Oncology and Applied Physics Departments at the University of Michigan, and Endectra LLC, a 2015 spinout from the University of Michigan which specializes in the development of novel radiation detectors utilizing SiPM technology and Cerenkov light analytics. In this project, Endectra will lead several on-body SiPM probe/array prototyping, scale-up, and testing cycles, while collaborating radiation oncology researchers provide device performance feedback, assess the advantages of CMSI over other commercial approaches, and test the hypothesis that improved detection of CE (at low photon counts) can yield improved utility in real-time tumor molecular characterization. Specific aims of this effort include the evaluation of CMSI-SiPM arrays for 1) their capacity to spectrally probe tumor molecular microenvironment and calibrate their performance in vitro using cell culture assays, and 2) their capacity to determine tumor aggressiveness/response and assess delivered dose in vivo using xenograft mouse models. We expect to demonstrate that CMSI can simultaneously determine delivered dose while spectroscopically characterizing tumor response to radiotherapy on a daily basis and in real time. If successful, Endectra could proceed to a Phase II effort including human trials, development of CMSI probes for multiple clinical applications, and development of the substantial commercial opportunity for this innovation in the radiotherapy equipment market. This would result in a paradigm shift in radiotherapy image-guidance, greatly improved patient safety and therapeutic impact, and a major improvement to public health.PROJECT NARRATIVE In this Phase I STTR, Endectra will work with oncology researchers at the University of Michigan to develop and evaluate a novel Cerenkov Multi-Spectral Imaging (CMSI) technique using new solid state on-body probes to conduct routine optical measurements of radiation dose and perform molecular imaging during cancer radiotherapy delivery. This approach is expected to provide more accurate tumor physiological representation and dose adaptation during treatment, reduce overall patient exposure to radiation, and allow for ongoing assessment of tumor physiological parameters. If successful, Endectra will develop CMSI as an alternative cost saving and effective molecular imaging/targeting modality for routine radiotherapy applications, greatly improving radiotherapy outcomes and yielding a major impact on public health.