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Towards Patient-Specific Treatment Planning of External Beam Radiotherapy Involving Radiosensitizers Using Nuclear Medicine Imaging

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D Adam

D Adam*, A Besemer , I Marsh , K Kloepping , L Hall , J Grudzinski , J Weichert , M Otto , B Bednarz , University of Wisconsin, Madison, WI


MO-AB-FS4-8 (Monday, July 31, 2017) 7:30 AM - 9:30 AM Room: Four Seasons 4

Purpose: Targeted radiosensitizers have the ability to achieve biological dose enhancements without necessitating tumor margin reductions that could potentially lead to increased toxicity in normal tissues. This work investigates the use of a priori PET/CT imaging of the biodistribution of a radiosensitizing compound in a patient and radiobiological modeling to determine the optimal combination of a targeted radiosensitizer and external beam radiotherapy.

Methods: A molarity-dependent dose modification factor (DMF) model was produced utilizing in vitro clonogenic assays of glioma cells with or without CLR1404 labeling. The DMF was determined by taking the ratio of the absorbed doses that resulted in 10% survival (control radiation dose divided by drug-treated radiation dose). Using the known specific activity of 124I-CLR1404 injected for the PET/CT scans, the 3D activity concentration distribution from PET was converted to a 3D molar concentration distribution of the drug. A 4 arc VMAT treatment plan was created to compare the dose distribution with and without the drug. By utilizing the molarity-dependent DMF model, DMF was calculated on a voxel by voxel basis and the resultant 3D dose distribution of the VMAT treatment plan was multiplied by the 3D DMF distribution, yielding the enhanced dose distribution. Subsequent optimization of the VMAT plan is possible to maximize PTV coverage and minimize OAR dose.

Results: Spatial distributions of the absorbed dose rates and dose volume histograms for each ROI were generated. After application of the dose enhancement factor, the absorbed dose in the tumor area increased by approximately 20% while still satisfying OAR constraints.

Conclusion: This work demonstrates the potential of explicitly increasing dose to tumors using CLR1404 as a radiosensitizer in conjunction with treatment plan optimization based upon the spatial distribution of the compound using radiolabeled 124I-CLR1404 in PET.

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