Prediction of time-integrated activity coefficients in PRRT using simulated dynamic PET and a pharmacokinetic model

Purpose To investigate the accuracy of predicted time-integrated activity coefficients (TIACs) in peptide-receptor radionuclide therapy (PRRT) using simulated dynamic PET data and a physiologically based pharmacokinetic (PBPK) model. Methods PBPK parameters were estimated using biokinetic data of 15 patients after injection of (152 ± 15) MBq of ¹¹¹In-DTPAOC (total peptide amount (5.78 ± 0.25) nmol). True mathematical phantoms of patients (MPPs) were the PBPK model with the estimated parameters. Dynamic PET measurements were simulated as being done after bolus injection of 150 MBq ⁶⁸Ga-DOTATATE using the true MPPs. Dynamic PET scans around 35 min p.i. (P₁), 4 h p.i. (P₂) and the combination of P₁ and P₂ (P₃) were simulated. Each measurement was simulated with four frames of 5 min each and 2 bed positions. PBPK parameters were fitted to the PET data to derive the PET-predicted MPPs. Therapy was simulated assuming an infusion of 5.1 GBq of ⁹⁰Y-DOTATATE over 30 min in both true and PET-predicted MPPs. TIACs of simulated therapy were calculated, true MPPs (true TIACs) and predicted MPPs (predicted TIACs) followed by the calculation of variabilities v. Results For P₁ and P₂ the population variabilities of kidneys, liver and spleen were acceptable (v < 10%). For the tumours and the remainders, the values were large (up to 25%). For P₃, population variabilities for all organs including the remainder further improved, except that of the tumour (v > 10%). Conclusion Treatment planning of PRRT based on dynamic PET data seems possible for the kidneys, liver and spleen using a PBPK model and patient specific information.