J Biomed Transl Res.
2020 Jun;21(2):79-90. 10.12729/jbtr.2020.21.2.079.
Radioisotope-ADME studies of Trastuzumab-monomethyl auristatin F in tumor bearing mice and healthy marmosets
- Affiliations
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- 1Department of Toxicology Evaluation, Graduate School of Konyang University, Daejeon 35365, Korea
- 2Department of Medicinal Biosciences, Konyang University, Nonsan 32992, Korea
- 3Laboratory Animal Center, Osong Medical Innovation Foundation, Cheongju 28160, Korea
- 4Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 56212, Korea
- 5Radiation Science and Technology, University of Science and Technology, Daejeon 34113, Korea
- 6ADC Platform & R2D Team, LegoChem Biosciences, Inc., Daejeon 34302, Korea
- KMID: 2503833
- DOI: http://doi.org/10.12729/jbtr.2020.21.2.079
Abstract
- Radioisotope ADME (RI-ADME) studies are enabling visualization of the biodistribution in molecular imaging. We applied RI-ADME to investigate the tumor targeting capacity and biodistribution of trastuzumab-monomethyl auristatin F (LCB14-0110) in JIMT-1 xenograft mice and healthy marmoset. The LCB14-0110 was labelled with 125I. 125I-LCB14-0110 was intravenously administered to the animals. The gamma-count and single-photon emission computed tomography/computed tomography (SPECT/CT) was conducted for biodistributioon and bioimaging of the biopharmaceutics. Tumor uptake in xenograft mice was highest at three-day after 125I-LCB14-0110 administration in both the biodistribution and SPECT/CT bioimaging. Alternatively, blood and organ tissues showed gradual decrease in radioactivity over time. In marmosets, radioactivity in all organ tissues rapidly reduced and no specific targeting of organs was observed in the biodistribution study and SPECT/CT imaging. Hence, 125ILCB14- 0110 demonstrated effective tumor targeting capacity and accumulated in JIMT-1 cell-bearing mice. However, accumulation did not occur in the organs of xenograft mice. Additionally, marmosets showed rapidly decrease in radioactivity throughout the entire body without accumulation in the normal organs. We also confirmed that the drug distribution was similar in normal organs between the two experimental animal species except spleen. Therefore, 125I is expected to be a useful tool in the study of RI-ADME in biopharmaceuticals through minimal antibody modification.
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