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Optimizing the Combination of Targeted Radionuclide Therapy Agents Using a Multi-Scale Patient-Specific Monte Carlo Dosimetry Platform

A Besemer

A Besemer1*, B Titz1,2, J Grudzinski1,2, J Weichert2,3, L Hall3, B Bednarz1, (1) Department of Medical Physics, University of Wisconsin-Madison, SMPH, Madison, WI (2) Cellectar Biosciences, Madison, WI (3) Department of Radiology, University of Wisconsin-Madison, SMPH, Madison, WI


SU-E-T-256 Sunday 3:00PM - 6:00PM Room: Exhibit Hall

Purpose: Combination targeted radionuclide therapy (TRT) is appealing because it can potentially exploit different mechanisms of action from multiple radionuclides as well as the variable dose rates due to the different radionuclide half-lives. The work describes the development of a multi-objective optimization algorithm to calculate the optimal ratio of radionuclide injection activities for delivery of combination TRT.
Methods: The ‘diapeutic’ (diagnostic and therapeutic) agent, CLR1404, was used as a proof-of-principle compound in this work. Isosteric iodine substitution in CLR1404 creates a molecular imaging agent when labeled with I-124 or a targeted radiotherapeutic agent when labeled with I-125 or I-131. PET/CT images of high grade glioma patients were acquired at 4.5, 24, and 48 hours post injection of 124I-CLR1404. The therapeutic 131I-CLR1404 and 125I-CLR1404 absorbed dose (AD) and biological effective dose (BED) were calculated for each patient using a patient-specific Monte Carlo dosimetry platform. The optimal ratio of injection activities for each radionuclide was calculated with a multi-objective optimization algorithm using the weighted sum method. Objective functions such as the tumor dose heterogeneity and the ratio of the normal tissue to tumor doses were minimized and the relative importance weights of each optimization function were varied.
Results: For each optimization function, the program outputs a Pareto surface map representing all possible combinations of radionuclide injection activities so that values that minimize the objective function can be visualized. A Pareto surface map of the weighted sum given a set of user-specified importance weights is also displayed. Additionally, the ratio of optimal injection activities as a function of the all possible importance weights is generated so that the user can select the optimal ratio based on the desired weights.
Conclusion: Multi-objective optimization of radionuclide injection activities can provide an invaluable tool for maximizing the dosimetric benefits in multi-radionuclide combination TRT.

Funding Support, Disclosures, and Conflict of Interest: BT, JG, and JW are affiliated with Cellectar Biosciences which owns the licensing rights to CLR1404 and related compounds.

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