Learning-enhanced hybrid planar-SPECT dosimetry for voxel-level Monte Carlo dose estimation in radionuclide therapy.

OBJECTIVE: Quantitative imaging-based dosimetry is essential for optimizing [177Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT), yet full multi-time-point (MTP) SPECT/CT is difficult to implement in routine clinical practice. This study proposes a hybrid planar-SPECT framework for organ-level TIA estimation and STP-constrained voxel-level Monte Carlo dose analysis from a single post-therapy SPECT/CT acquisition. APPROACH: The proposed framework integrates single-time-point (STP) SPECT/CT with serial planar imaging to derive organ-level time-integrated activities (TIAs). A physics-informed support vector regression (SVR) model is incorporated to refine planar-to-SPECT scaling factors and improve the robustness of planar-derived activity quantification. The resulting organ TIAs are used to scale the fixed within-organ STP SPECT pattern and generate voxelized TIA maps as source distributions for Monte Carlo (MC)-based dose calculation. The method is evaluated against reference MTP SPECT/CT data in 11 patients and further applied to a separate cohort of 23 patients to explore vertebral dose heterogeneity and its association with hematologic toxicity. MAIN RESULTS: Hybrid dosimetry showed good agreement with MTP SPECT/CT, with organ-level errors of approximately 10-15%. The SVR-based refinement modestly reduced scaling bias, particularly in anatomically challenging structures. Voxel-level vertebral dose heterogeneity metrics showed moderate but exploratory correlations with hematologic toxicity (ρ ≈ 0.4-0.5) after false-discovery-rate correction, whereas conventional organ-averaged dose metrics showed no significant association. SIGNIFICANCE: The proposed hybrid planar-SPECT framework supports clinically feasible organ-level dosimetry from a reduced acquisition protocol. The resulting voxelized maps provide STP-constrained approximate source distributions for MC dose calculation and exploratory characterization of spatial dose heterogeneity, rather than reconstructions of time-varying MTP voxel kinetics. The SVR improvement observed in the 11-patient internal validation remains preliminary, requiring larger cohorts for robustness and external validation for generalizability.