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

Abstract

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 150MBq ⁶⁸Ga-DOTATATE using the true MPPs. Dynamic PET scans around 35min p.i. (P₁), 4h p.i. (P₂) and the combination of P₁ and P₂ (P₃) were simulated. Each measurement was simulated with four frames of 5min 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 5.1GBq of ⁹⁰Y-DOTATATE over 30min 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.

Keywords: Dynamic PET; PBPK model; PET noise model; PRRT treatment planning.