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.