title: Physiologically Based Pharmacokinetic (PBPK) Model for Biodistribution of Radiolabeled Peptides in Patients with Neuroendocrine Tumours.
abstract: OBJECTIVE
  The objectives of this work was to assess the benefits of the application of Physiologically Based Pharmacokinetic (PBPK) models in patients with different neuroendocrine tumours (NET) who were treated with Lu-177 DOTATATE. The model utilises clinical data on biodistribution of radiolabeled peptides (RLPs) obtained by whole body scintigraphy (WBS) of the patients.
  
  
  METHODS
  The blood flow restricted (perfusion rate limited) type of the PBPK model for biodistribution of radiolabeled peptides (RLPs) in individual human organs is based on the multi-compartment approach, which takes into account the main physiological processes in the organism: absorption, distribution, metabolism and excretion (ADME). The approach calibrates the PBPK model for each patient in order to increase the accuracy of the dose estimation. Datasets obtained using WBS in four patients have been used to obtain the unknown model parameters. The scintigraphic data were acquired using a double head gamma camera in patients with different neuroendocrine tumours who were treated with Lu-177 DOTATATE. The activity administered to each patient was 7400 MBq.
  
  
  RESULTS
  Satisfactory agreement of the model predictions with the data obtained from the WBS for each patient has been achieved.
  
  
  CONCLUSIONS
  The study indicates that the PBPK model can be used for more accurate calculation of biodistribution and absorbed doses in patients. This approach is the first attempt of utilizing scintigraphic data in PBPK models, which was obtained during Lu-177 peptide therapy of patients with NET.
authors.affiliation: Ascend Technologies Ltd, Eastleigh, UK; Faculty of Civil Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Radovan
authors.initials: R
authors.lastname: Gospavic
authors.affiliation: Institute of Nuclear Medicine with PET-Center, Wilhelminenspital, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Knoll
authors.affiliation: Institute of Nuclear Medicine with PET-Center, Wilhelminenspital, Vienna, Austria.
authors.forename: Siroos
authors.initials: S
authors.lastname: Mirzaei
authors.affiliation: Ascend Technologies Ltd, Eastleigh, UK.
authors.forename: Viktor
authors.initials: V
authors.lastname: Popov
keywords: Lu-177 DOTATATE; PBPK model; Radiolabeled peptides; Whole body scintigraphy