Deep Learning for Automated Measures of SUV and Molecular Tumor Volume in [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL, [¹⁸F]FDG, and...

Metastatic castration-resistant prostate cancer has a high rate of mortality with a limited number of effective treatments after hormone therapy. Radiopharmaceutical therapy with [¹⁷⁷Lu]Lu-prostate-specific membrane antigen-617 (LuPSMA) is one treatment option; however, response varies and is partly predicted by PSMA expression and metabolic activity, assessed on [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL and [¹⁸F]FDG PET, respectively. Automated methods to measure these on PET imaging have previously yielded modest accuracy. Refining computational workflows and standardizing approaches may improve patient selection and prognostication for LuPSMA therapy. Methods: PET/CT and quantitative SPECT/CT images from an institutional cohort of patients staged for LuPSMA therapy were annotated for total disease burden. In total, 676 [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL PET, 390 [¹⁸F]FDG PET, and 477 LuPSMA SPECT images were used for development of automated workflow and tested on 56 cases with externally referred PET/CT staging. A segmentation framework, the Global Threshold Regional Consensus Network, was developed based on nnU-Net, with processing refinements to improve boundary definition and overall label accuracy. Results: Using the model to contour disease extent, the mean volumetric Dice similarity coefficient for [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL PET was 0.94, for [¹⁸F]FDG PET was 0.84, and for LuPSMA SPECT was 0.97. On external test cases, Dice accuracy was 0.95 and 0.84 on PSMA and FDG PET, respectively. The refined models yielded consistent improvements compared with nnU-Net, with an increase of 3%-5% in Dice accuracy and 10%-17% in surface agreement. Quantitative biomarkers were compared with a human-defined ground truth using the Pearson coefficient, with scores for [⁶⁸Ga]PSMA-11 or [¹⁸F]DCFPyL, [¹⁸F]FDG, and LuPSMA, respectively, of 0.98, 0.94, and 0.99 for disease volume; 0.98, 0.88, and 0.99 for SUV_mean; 0.96, 0.91, and 0.99 for SUV_max; and 0.97, 0.96, and 0.99 for volume intensity product. Conclusion: Delineation of disease extent and tracer avidity can be performed with a high degree of accuracy using automated deep learning methods. By incorporating threshold-based postprocessing, the tools can closely match the output of manual workflows. Pretrained models and scripts to adapt to institutional data are provided for open use.