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Clinical Trial
. 2018 Oct 5;8(1):14860.
doi: 10.1038/s41598-018-33160-0.

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

F Morschhauser  1   2 , B Dekyndt  3   4 , C Baillet  3   5 , C Barthélémy  3 , E Malek  3 , J Fulcrand  3 , P Bigot  3 , D Huglo  5 , B Décaudin  3   4 , N Simon  3   4 , P Odou  3   4
Affiliations
Clinical Trial

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

F Morschhauser et al. Sci Rep. .

Abstract

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 90Y-Ibritumomab tiuxetan (90Y-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 90Y-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 111In-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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Subtraction of the blood constituent of Ibritumomab tiuxetan from total organ to obtain the remaining tissue constituent
Figure 2
Figure 2
Evolution of 111In-IT concentration in blood and organ tissues.
Figure 3
Figure 3
Model selected for best biodistribution fit.
Figure 4
Figure 4
FIZZ trial design.
See this image and copyright information in PMC

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