Physiologically Based Pharmacokinetic (PBPK) model for biodistribution of radiolabeled peptides in patients with neuroendocrine tumours

Document Type: Original Article

Authors

1 Ascend Technologies Ltd, Eastleigh, UK

2 Faculty of Civil Engineering, University of Belgrade, Belgrade, Serbia

3 Institute of Nuclear Medicine with PET-Center, Wilhelminenspital, Vienna, Austria

10.7508/aojnmb.2016.02.005

Abstract

Objective(s): 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 7400MBq.
Results: Satisfactory agreement of the model predictions with the data obtained from the WBS for each patient has been achieved. Conclusion: 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.

Keywords

Main Subjects


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