Single-time-point estimation of absorbed doses in PRRT using a non-linear mixed-effects model.

Area of Science:

• Nuclear Medicine
• Radiopharmaceutical Therapy
• Medical Physics

Background:

• Accurate dosimetry is crucial for effective peptide-receptor radionuclide therapy (PRRT) treatment planning.
• Time-integrated activity coefficients (TIACs) and absorbed doses (ADs) are key parameters for dosimetry.
• Current methods can be complex, necessitating simplified approaches.

Purpose of the Study:

• To evaluate a simplified dosimetry method for ⁹⁰Y-DOTATATE PRRT.
• To assess the accuracy of using a physiologically-based pharmacokinetic (PBPK) model, a nonlinear mixed-effect (NLME) model, and single-time-point imaging.
• To determine if TIACs and ADs can be reliably calculated from limited data in organs and tumors.

Main Methods:

• Biokinetic data from eight patients using ¹¹¹In-DOTATATE scintigraphy were analyzed.
• PBPK and NLME models were employed with single-time-point imaging data.
• Calculated TIACs and ADs were compared against those derived from all-time-point data.
• Relative deviations (RDs) and root mean square errors (RMSE) were used for accuracy assessment.

Main Results:

• The PBPK and NLME models demonstrated good fits with biokinetic measurements.
• Time point T4 (46.7 ± 1.7 h post-injection) showed low median RDs for TIACs in kidneys (5%) and tumors (2%).
• T4 also yielded the lowest joint RMSE for absorbed doses, indicating optimal accuracy for kidney and tumor dosimetry.
• The simplified approach showed performance comparable to established methods like the sum of exponentials (SOE).

Conclusions:

• A simplified dosimetry approach using PBPK, NLME models, and single-time-point imaging is feasible for PRRT.
• A single post-injection measurement may suffice for calculating TIACs and ADs in kidneys and tumors.
• This simplification can aid in more efficient and accurate PRRT treatment planning.