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KMID : 1147220200210020079
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Journal of Biomedical and Translational Research
2020 Volume.21 No. 2 p.79 ~ p.90
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Radioisotope-ADME studies of Trastuzumab-monomethyl auristatin F in tumor bearing mice and healthy marmosets
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Lee Hye-Won
Jeong Yun-Ha
Hwang Jin-Ah
Lee Jae-Jun
Yu A-Ram
Kang Jung-Ae
Raza Muhammad Asim
Park Sang-Hyun
Park Yun-Hee
Kim Dong-Hwan
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Abstract
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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, 125I-LCB14-0110 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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KEYWORD
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radioisotope ADME (RI-ADME), biodistribution, trastuzumab-monomethyl auristatin F (trastuzumab-MMAF), single-photon emission computed tomography/computed tomography (SPECT/CT), marmoset
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