Sensing Collimator Technology for Ultrasensitive SPECT Imaging of Targeted Radiopharmaceutical Therapies

Project Summary This application addresses critically unmet needs in the field of targeted radiopharmaceutical therapy, an emerging treatment paradigm for metastatic cancers. Therapeutic radiopharmaceuticals localize to and deposit cytotoxic beta and alpha particles at sites of disease. Despite the great potential of these cytotoxic emitters, a one-size-fits-all approach is used to determine administered activities that ignores features of an individual’s disease phenotype. Precision and personalized dosimetry is a long-sought goal that is complicated by the inherently low imaging signal produced by these therapeutic radionuclides and low administered activities used for these drugs. For example, in contrast to diagnostic procedures, the administered activities of alpha particle therapies are in the 100 µCi range, orders of magnitude lower than a typical SPECT or PET imaging agent; and isotopes of interest (Actinium-225, Radium-223 and Lead-212) release only 5% of their decay energy by photons. At such low photon fluxes, it is crucial to collect as many photons as possible in order to reconstruct accurate, precise, and high-resolution imaging data. Conventional SPECT systems employ a lead collimator (to provide positional information) in front of a NaI(Tl) crystal based camera (with optimal sensitivity for the detection of ~140keV photons). Such a device is sufficient for diagnostic imaging with Tc-99m despite rejection of 99% of incident photons. Here, we develop a novel imaging detector module in which the collimator section is composed of active sensing detectors to provide spatial and directional information without rejecting photons. Predicated on extensive preliminary data and proof of concept prototype detectors we put forwards a mathematic framework using accurate physics and state-of-the-art anthropomorphic models to optimize this Sensing-Collimator Imaging (SCI) SPECT technology. We rigorously validate and evaluate this platform in order to develop the next generation SPECT imager that can reliably measure the distribution of therapeutic radiopharmaceuticals with orders of magnitude greater sensitivity and innovate the field towards the goal of direct, sensitive, and accurate imaging of alpha-emitting targeted radiopharmaceutical therapies.