Internal radiation dosimetry of a <sup>152</sup>Tb-labeled antibody in tumor-bearing mice.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_22C26DF26A4B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Internal radiation dosimetry of a <sup>152</sup>Tb-labeled antibody in tumor-bearing mice.
Journal
EJNMMI research
Author(s)
Cicone F., Gnesin S., Denoël T., Stora T., van der Meulen N.P., Müller C., Vermeulen C., Benešová M., Köster U., Johnston K., Amato E., Auditore L., Coukos G., Stabin M., Schaefer N., Viertl D., Prior J.O.
ISSN
2191-219X (Print)
Publication state
Published
Issued date
11/06/2019
Peer-reviewed
Oui
Volume
9
Number
1
Pages
53
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Biodistribution studies based on organ harvesting represent the gold standard pre-clinical technique for dose extrapolations. However, sequential imaging is becoming increasingly popular as it allows the extraction of longitudinal data from single animals, and a direct correlation with deterministic radiation effects. We assessed the feasibility of mouse-specific, microPET-based dosimetry of an antibody fragment labeled with the positron emitter <sup>152</sup> Tb [(T <sub>1/2</sub> = 17.5 h, Eβ <sup>+</sup> mean = 1140 keV (20.3%)]. Image-based absorbed dose estimates were compared with those obtained from the extrapolation to <sup>152</sup> Tb of a classical biodistribution experiment using the same antibody fragment labeled with <sup>111</sup> In. <sup>152</sup> Tb was produced by proton-induced spallation in a tantalum target, followed by mass separation and cation exchange chromatography. The endosialin-targeting scFv78-Fc fusion protein was conjugated with the chelator p-SCN-Bn-CHX-A"-DTPA, followed by labeling with either <sup>152</sup> Tb or <sup>111</sup> In. Micro-PET images of four immunodeficient female mice bearing RD-ES tumor xenografts were acquired 4, 24, and 48 h after the i.v. injection of <sup>152</sup> Tb-CHX-DTPA-scFv78-Fc. After count/activity camera calibration, time-integrated activity coefficients (TIACs) were obtained for the following compartments: heart, lungs, liver, kidneys, intestines, tumor, and whole body, manually segmented on CT. For comparison, radiation dose estimates of <sup>152</sup> Tb-CHX-DTPA-scFv78-Fc were extrapolated from mice dissected 4, 24, 48, and 96 h after the injection of <sup>111</sup> In-CHX-DTPA-scFv78-Fc (3-5 mice per group). Imaging-derived and biodistribution-derived organ TIACs were used as input in the 25 g mouse model of OLINDA/EXM® 2.0, after appropriate mass rescaling. Tumor absorbed doses were obtained using the OLINDA2 sphere model. Finally, the relative percent difference (RD%) between absorbed doses obtained from imaging and biodistribution were calculated.
RD% between microPET-based dosimetry and biodistribution-based dose extrapolations were + 12, - 14, and + 17 for the liver, the kidneys, and the tumors, respectively. Compared to biodistribution, the imaging method significantly overestimates the absorbed doses to the heart and the lungs (+ 89 and + 117% dose difference, respectively).
MicroPET-based dosimetry of <sup>152</sup> Tb is feasible, and the comparison with organ harvesting resulted in acceptable dose discrepancies for body districts that can be segmented on CT. These encouraging results warrant additional validation using radiolabeled biomolecules with a different biodistribution pattern.
Keywords
152Tb, Biodistribution, Murine phantoms, OLINDA/EXM® 2.0, Organ harvesting, Radiolabeled monoclonal antibodies, Small animal dosimetry, Spherical model, TEM-1, microPET
Pubmed
Web of science
Open Access
Yes
Create date
24/06/2019 7:04
Last modification date
15/01/2021 7:08
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