3D Monte Carlo bone marrow dosimetry for Lu-177-PSMA therapy with guidance of non-invasive 3D localization of active bone marrow via Tc-99m-anti-granulocyte antibody SPECT/CT

摘要

BackgroundThe bone marrow (BM) is a main risk organ during Lu-177-PSMA ligand therapy of metastasized castration-resistant prostate cancer (mCRPC) patients. So far, BM dosimetry relies on S values, which are pre-computed for reference anatomies, simplified activity distributions, and a physiological BM distribution. However, mCRPC patients may show a considerable bone lesion load, which leads to a heterogeneous and patient-specific activity accumulation close to BM-bearing sites. Furthermore, the patient-specific BM distribution might be significantly altered in the presence of bone lesions. The aim was to perform BM absorbed dose calculations through Monte Carlo (MC) simulations and to investigate the potential value of image-based BM localization.This study is based on 11 Lu-177-PSMA-617 therapy cycles of 10 patients (10 first cycles), who obtained a pre-therapeutic Ga-68-PSMA-11 PET/CT; quantitative Lu-177 SPECT acquisitions of the abdomen 24 (+CT), 48, and 72 h p.i.; and a Lu-177 whole-body planar acquisition at 24 h post-therapy. Patient-specific 3D volumes of interest were segmented from the Ga-68-PSMA-11 PET/CT, filled with activity information from the Lu-177 data, and imported into the FLUKA MC code together with the patient CT. MC simulations of the BM absorbed dose were performed assuming a physiological BM distribution according to the ICRP 110 reference male (MC1) or a displacement of active BM from the direct location of bone lesions (MC2). Results were compared with those from S values (SMIRD). BM absorbed doses were correlated with the decrease of lymphocytes, total white blood cells, hemoglobin level, and platelets. For two patients, an additional pre-therapeutic Tc-99m-anti-granulocyte antibody SPECT/CT was performed for BM localization.