title: Time-integrated activity coefficient estimation for radionuclide therapy using PET and a pharmacokinetic model: A simulation study on the effect of sampling schedule and noise.
abstract: OBJECTIVE
  The aim of this study was to investigate the accuracy of PET-based treatment planning for predicting the time-integrated activity coefficients (TIACs).
  
  
  METHODS
  The parameters of a physiologically based pharmacokinetic (PBPK) model were fitted to the biokinetic data of 15 patients to derive assumed true parameters and were used to construct true mathematical patient phantoms (MPPs). Biokinetics of 150 MBq (68)Ga-DOTATATE-PET was simulated with different noise levels [fractional standard deviation (FSD) 10%, 1%, 0.1%, and 0.01%], and seven combinations of measurements at 30 min, 1 h, and 4 h p.i. PBPK model parameters were fitted to the simulated noisy PET data using population-based Bayesian parameters to construct predicted MPPs. Therapy simulations were performed as 30 min infusion of (90)Y-DOTATATE of 3.3 GBq in both true and predicted MPPs. Prediction accuracy was then calculated as relative variability vorgan between TIACs from both MPPs.
  
  
  RESULTS
  Large variability values of one time-point protocols [e.g., FSD = 1%, 240 min p.i., vkidneys = (9 ± 6)%, and vtumor = (27 ± 26)%] show inaccurate prediction. Accurate TIAC prediction of the kidneys was obtained for the case of two measurements (1 and 4 h p.i.), e.g., FSD = 1%, vkidneys = (7 ± 3)%, and vtumor = (22 ± 10)%, or three measurements, e.g., FSD = 1%, vkidneys = (7 ± 3)%, and vtumor = (22 ± 9)%.
  
  
  CONCLUSIONS
  (68)Ga-DOTATATE-PET measurements could possibly be used to predict the TIACs of (90)Y-DOTATATE when using a PBPK model and population-based Bayesian parameters. The two time-point measurement at 1 and 4 h p.i. with a noise up to FSD = 1% allows an accurate prediction of the TIACs in kidneys.
authors: Medical Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Mannheim 68167, Germany and Department of Radiation Oncology, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Mannheim 68167, Germany.
authors: Deni
authors: D
authors: Hardiansyah
authors: Medical Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Mannheim 68167, Germany.
authors: Wei
authors: W
authors: Guo
authors: Department of Nuclear Medicine, Ulm University, Ulm 89081, Germany.
authors: Peter
authors: P
authors: Kletting
authors: Department of Nuclear Medicine, University Hospital, RWTH Aachen University, Aachen 52074, Germany and Department of Nuclear Medicine, Maastricht University Medical Center (MUMC+), Maastricht 6229, The Netherlands.
authors: Felix M
authors: FM
authors: Mottaghy
authors: Medical Radiation Physics/Radiation Protection, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Mannheim 68167, Germany.
authors: Gerhard
authors: G
authors: Glatting
mesh_terms: D001499:Bayes Theorem; D006801:Humans; D008954:Models, Biological; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy*; D009942:Organometallic Compounds / Q000493:pharmacokinetics; D019047:Phantoms, Imaging; D049268:Positron-Emission Tomography; D011880:Radiotherapy Planning, Computer-Assisted; D059629:Signal-To-Noise Ratio; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D009942:Organometallic Compounds; C513399:gallium Ga 68 dotatate