Hyperspectral Single Photon Imaging of Targeted Alpha-Emitters

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Targeted alpha-emitter therapy (TAT) is an emerging modality in the cancer therapy. By directly killing cancer cells it is less susceptible to development of resistance. Combination of external beam radiation therapy (XRT) and TATs have a high potential for treatment of systemic disease: the XRT is effective for a small number of large tumors, and the TAT for small, widely disseminated metastases. To understand the targeting behavior and dose response, dosimetry information is required in preclinical and early-stage clinical studies. Estimates of the dose distribution are essential for optimal planning of TAT alone and combined with XRT. Knowledge of the dose distribution from TATs could shorten clinical trials by helping select patients for whom the therapy is most likely to be effective, and by shortening Phase 1 dose escalation trials by using knowledge of toxicities obtained from XRT experience. The distribution of the radionuclide in vivo is a prerequisite for estimating TAT dose distribution. For alpha emitters, there are several significant challenges. Due to their high linear energy transfer and resulting lethality, low doses are commonly used. Also, the spectrum typically has many low-abundance gamma rays spread over a wide energy range combined with characteristic x-rays. Typical decay chains include multiple daughter radionuclides, and it is important to estimate their activity distributions. These capabilities would be enabled by an advanced SPECT system with high sensitivity and high spatial and energy resolution. In this project, we will develop the Alpha-SPECT system, a novel scanner aimed at imaging of these radionuclides. It uses advanced spectroscopic CZT imaging detectors to provide excellent spatial resolution, ultrahigh sensitivity, and excellent energy resolution of these radionuclides in large animals. To achieve this, we will push the forefront of CZT detector technology a generation ahead of the current state-of-art commercial CZT-based gamma-ray detectors. We will combine this CZT-based detection system with the novel synthetic compound-eye gamma camera design to realize the Alpha-SPECT system. We will develop quantitative reconstruction methods and web-based interface for this system to estimate the distribution of the parent and daughter radionuclides. Finally, we will evaluate the system and reconstruction method using phantom and large animal imaging studies using TATs that are currently under development at Johns Hopkins to validate the system. We will market access to the system as a core service to the cancer research community through Johns Hopkins and, through Rapid, LLC, to commercial drug developers. This project will not only serve as a critical step to bring the unique spectral SPECT imaging capability to end users who are currently developing targeted radionuclide therapies, but it also will potentially lead to a state-of-art spectral-CZT detector platform for use by the research community and industry in developing the next generation clinical SPECT instrumentations for applications beyond targeted radionuclide therapies. This prosed project has a clear pathway to serve a much broader spectrum of end-users.