⁶⁴Cu-ATSM internal dosimetry in a computational tumor-bearing mouse model

Witter, Paige, author
Brandl, Alexander, advisor
Leary, Del, committee member
Stallones, Lorann, committee member
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The radiopharmaceutical Copper-64 diacetyl-bis(N4-methylthiosemicarbazones) (64Cu-ATSM) has growing clinical interest as a theragnostic agent; that is, one that can be used as both a diagnostic tool and a treatment for certain tumors. The ATSM ligand selectively distributes to hypoxic tissues, traditionally difficult targets for chemotherapy and radiotherapy cancer treatments. The copper radionuclide dissociates in the reducing environment, at which point the unique decay scheme of 64Cu offers multiple imaging and clinical pathways. Using an anatomically accurate voxelized phantom of a cancer-bearing mouse, a Monte Carlo N-Particle (MCNP) radiation transport code assessment of absorbed fractions and absorbed dose to major organs was carried out. In decay scenarios in which the organ of interest was the source organ, approximately 60% of the total energy transferred from a 64Cu decay came from the beta decay, approximately 30% from the positron decay, and approximately 1% from the Auger electrons. These results were used in conjunction with 64Cu-ATSM biodistribution data from two published studies to estimate organ and whole-body absorbed doses from administered activities. The differences in organ absorbed doses between the studies shows the mouse model variances that can impact dose and lead to variability in dose-response curves down the line. An MCNP model allows for a better understanding of the organ-specific doses and should be considered in the development of future studies assessing the theragnostic properties of 64Cu-ATSM in translational models while sparing these models' healthy organs and tissues.
2021 Spring.
Includes bibliographical references.
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