Abstract
Biologically-targeted alpha-particle radiation is the basis of new and promising treatments for eliminating disseminated micrometastases and the residual microscopic malignancies that remain after surgery or radiation therapy. The short-range alpha-particles are highly cytotoxic and capable of inactivating single, isolated cancer cells which may otherwise cause recurrence. Astatine-211 is a promising alpha emitter for therapy; the 7.2 hour half-life of 211 At provides sufficient time for biological-targeting to take place. However, this radionuclide is in short supply and future treatment strategies still require extensive preclinical evaluation. The present work aims to develop technologies that (1) increase the world-wide availability of 211 At for clinical use, and (2) assess the risks of 211 At-based therapies by quantifying the activity distributions in animal models. At TRIUMF (Vancouver, BC), the feasibility of a novel generator system for 211 At is under investigation which would allow distribution of 211 At across Canada and internationally. Briefly, a longer-lived parent radionuclide of 211 At, radon-211, would be produced and allowed to decay in containment to yield 211 At in solution. Additionally, a supplementary study is underway in collaboration with the University of Washington to evaluate the sub-organ biodistributions of astatinated targeting biomolecules, with cell-level resolution. These measurements involve high resolution quantitative alpha-particle imaging in thin tissue samples and can be done for a selection of applications (eg. lymphoma, metastatic prostate cancer, etc) using animal models. The planned alpha-camera measurements are primarily designed to predict and assess the risk of toxicity associated with 211 At-based therapies and aid in developing the future clinical applications.
Published Version
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