Machine Learning-Based Noninvasive Quantification of Single-Imaging Session Dual-Tracer ¹⁸F-FDG and ⁶⁸Ga-DOTATATE Dynamic PET-CT in Oncology

68Ga-DOTATATE PET-CT is routinely used for imaging neuroendocrine tumor (NET) somatostatin receptor subtype 2 (SSTR2) density in patients, and is complementary to FDG PET-CT for improving the accuracy of NET detection, characterization, grading, staging, and predicting/monitoring NET responses to treatment. Performing sequential 18F-FDG and 68Ga-DOTATATE PET scans would require 2 or more days and can delay patient care. To align temporal and spatial measurements of 18F-FDG and 68Ga-DOTATATE PET, and to reduce scan time and CT radiation exposure to patients, we propose a single-imaging session dual-tracer dynamic PET acquisition protocol in the study. A recurrent extreme gradient boosting (rXGBoost) machine learning algorithm was proposed to separate the mixed 18F-FDG and 68Ga-DOTATATE time activity curves (TACs) for the region of interest (ROI) based quantification with tracer kinetic modeling. A conventional parallel multi-tracer compartment modeling method was also implemented for reference. Single-scan dual-tracer dynamic PET was simulated from 12 NET patient studies with 18F-FDG and 68Ga-DOTATATE 45-min dynamic PET scans separately obtained within 2 days. Our experimental results suggested an 18F-FDG injection first followed by 68Ga-DOTATATE with a minimum 5 min delayed injection protocol for the separation of mixed 18F-FDG and 68Ga-DOTATATE TACs using rXGBoost algorithm followed by tracer kinetic modeling is highly feasible.