A new pharmacokinetic model for 90 Y-ibritumomab tiuxetan based on 3-dimensional dosimetry

Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequentia...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2018-10, Vol.8 (1), p.14860
Main Authors: Morschhauser, F, Dekyndt, B, Baillet, C, Barthélémy, C, Malek, E, Fulcrand, J, Bigot, P, Huglo, D, Décaudin, B, Simon, N, Odou, P
Format: Article
Language:English
Subjects:
Life Sciences
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Monoclonal antibodies (mAbs) are key components in several therapies for cancer and inflammatory diseases but current knowledge of their clinical pharmacokinetics and distribution in human tissues remains incomplete. Consequently, optimal dosing and scheduling in clinics are affected. With sequential radiolabeled mAb-based imaging, radiation dosing in tissues/organs can be calculated to provide a better assessment of mAb concentrations in tissues. This is the first pharmacokinetic model of Y-Ibritumomab tiuxetan ( Y-IT) in humans to be described, based on three-dimensional (3D) dosimetry using single-photon emission computed-tomography coupled with computed-tomography. 19 patients with follicular lymphoma were treated initially with Y-IT in the FIZZ trial. Based on a compartmental approach individualising the vascular compartment within studied organs, this study proposes a reliable pharmacokinetic (PK) five-compartment model replacing the currently used two-compartment model and constitutes a new direction for further research. This model provides exchange constants between the different tissues, Area Under the Curve of In-IT in blood (AUC) and Mean Residence Time (MRT) that have not been reported so far for IT. Finally, the elimination process appears to occur in a compartment other than the liver or the spleen and suggests the metabolism of mAbs may take place mainly on the vascular compartment level.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-33160-0