Single-time-point tumor dosimetry using population-based model selection and nonlinear mixed-effects modeling in...

Area of Science:

• Nuclear Medicine
• Radiopharmacology
• Oncology

Background:

• Molecular radiotherapy with [177Lu]Lu-PSMA-617 is a key treatment for metastatic castration-resistant prostate cancer.
• Accurate dosimetry is crucial for optimizing treatment efficacy and minimizing toxicity.
• Standard dosimetry involves multiple imaging sessions, presenting logistical challenges; single-time-point (STP) dosimetry offers a practical alternative but faces challenges with tumor kinetics and inter-patient variability.

Purpose of the Study:

• To assess the accuracy of STP tumor dosimetry using SPECT/CT, PBMS, and an NLME model in a large patient cohort.
• To evaluate diverse biokinetic measurements for [177Lu]Lu-PSMA-617 therapy.

Main Methods:

• Collected biokinetic data from 49 patients with metastatic castration-resistant prostate cancer using SPECT/CT at multiple time points post-[177Lu]Lu-PSMA-617 injection.
• Fitted ten different exponential functions to tumor biokinetic data using an NLME framework, incorporating fixed and random effects.
• Employed PBMS with goodness-of-fit tests and Akaike weights to select the optimal function, then calculated reference and STP time-integrated activities per volume (TIAVs) for comparison with the Hänscheid method.

Main Results:

• The function f(t) = A1*e^-(λ1+λphys)*t + A2*e^-(λphys)*t - (A1+A2)*e^-(λ2+λphys)*t was selected by PBMS with 93% Akaike weight.
• STP dosimetry using a single SPECT/CT measurement at approximately 66.3 hours post-injection yielded a mean relative deviation (RD) of 0.5% ± 11.0% compared to reference TIAVs.
• The NLME-based STP dosimetry method demonstrated superior accuracy over the Hänscheid method across all evaluated time points, with RMSEs for STP TIAV RDs ranging from 11% to 53% across time points 1-5.

Conclusions:

• A single SPECT/CT measurement around 3 days post-injection can effectively estimate tumor TIAVs in [177Lu]Lu-PSMA-617 therapy.
• The NLME method combined with PBMS offers a robust approach for simplified, accurate dosimetry in clinical practice.