Ultra-low-dose in vivo imaging in stem cell-enabled brain tumor theranostics using an optimized CZT-microSPECT scanner
Abstract
Neural stem cells (NSCs) show significant therapeutic potential for targeted delivery of agents to brain tumors due to their intrinsic tropism and ability to cross the blood-brain barrier. However, the lack of a reliable, high-sensitivity method for non-invasive, in vivo NSC monitoring and tracking hinders the development of NSC-based therapies. We present the characterization, optimization and in vivo validation of the CZT-microSPECT system for high-sensitivity tracking of small populations of radiolabeled NSCs. The stationary CZT-microSPECT scanner, based on solid-state detectors and a custom-designed tungsten collimator, has been tested for imaging ultra-low activities of iodine-125 (125I; < 2.5 μCi) offering sub-keV energy resolution. Its unique design enables the system to act as 96 concurrent gamma cameras. We investigated the system’s high resolution and high sensitivity through Monte Carlo simulations and a preclinical longitudinal animal study. In the in vivo mouse study, the system successfully detected small clusters of radiolabeled NSCs with ultra-low injected activities (ranging between 0.6 and 2.56 μCi) in as little as 5 minutes imaging time. The system also captured the migration of NSCs from the injection site to distant metastatic locations. This work demonstrates the potential of ultra-low-dose SPECT imaging in developing and optimizing NSC-enabled theranostics of brain tumor.
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