Gastrointestinal Dosimetry of 177lu-PSMA-617 Radiopharmaceutical Therapy In Metastatic Prostate Cancer Patients: Results from a Single-Center Retrospective Study
Abstract
Purpose
Gastrointestinal (GI) adverse events following 177Lu-PSMA radiopharmaceutical therapy (RPT) occur frequently, including nausea, vomiting, constipation, and diarrhea (occurring in 19-35% of patients). Despite the frequent occurrence of GI-related toxicities, to date, comprehensive dosimetry has not been reported. GI dosimetry remains challenging due to the complex anatomy of the GI tract, heterogeneous uptake, and modeling of clearance kinetics. In this work, we used multiple time point post-therapy imaging to quantify absorbed doses across five bowel segments to enable correlations with adverse event incidence.
Methods
We included 43 patients from the phase 2 RESIST-PC trial (NCT03042312) who underwent 177Lu-PSMA-617 therapy and serial post-therapy imaging. We used a hybrid planar/SPECT protocol with whole-body planar images acquired at 4, 24, 48 and 72–168 hours post-injection, with a single quantitative SPECT/CT at 24 hours. Absorbed doses were calculated using MIM SurePlan MRT with a hybrid planar/SPECT time–activity workflow. The GI tract was manually segmented into five regions by an experienced physician: ascending, transverse, descending colon, small bowel, and rectosigmoid. Each region was propagated onto the planar series to generate time-activity curves using trapezoidal integration. Absorbed doses were estimated using a voxelized S-value dose kernel for 177Lu. GI related adverse events were recorded to explore potential dose–toxicity relationships.
Results
The preliminary analysis includes 21 patients with complete imaging data. Median (range) absorbed doses were 0.229 (0.104–1.022), 0.167 (0.039-1.411), 0.133 (0.031-1.720), 0.152 (0.049–0.328), and 0.079 (0.017–1.027) Gy/GBq for ascending colon, transverse colon, descending colon, small bowel, and rectosigmoid, respectively. Heterogeneity was observed across GI segments, and across patients.
Conclusion
In this work, we report patient-specific absorbed dose estimates for the GI tract in patients treated with 177Lu-PSMA-617. Absorbed doses were heterogeneous across GI segments, and between patients, enabling future work exploring correlations with acute adverse events.