tetano
Editor, Senior Moderator
Mol Pharm
. 2023 Jan 20.
doi: 10.1021/acs.molpharmaceut.2c00954. Online ahead of print.
Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with [SUP]131[/SUP]I-Labeling and SPECT Imaging
Jiajun Ye[SUP] 1 [/SUP], Weidong Yang[SUP] 1 [/SUP], Zhaojuan Xie[SUP] 1 [/SUP], Yuhao Yan[SUP] 1 [/SUP], Guoquan Li[SUP] 1 [/SUP], Guiyu Li[SUP] 1 [/SUP], Xiang Li[SUP] 1 [/SUP], Wenhui Ma[SUP] 1 [/SUP], Fei Kang[SUP] 1 [/SUP], Mingru Zhang[SUP] 1 [/SUP], Jing Wang[SUP] 1 [/SUP]
Affiliations
Abstract
Coronavirus disease 2019 (COVID-19) is a serious threat to public health and is in urgent need of specific drugs. Meplazumab, a humanized monoclonal antibody targeting CD147, was confirmed to competitively block the binding between the spike of syndrome coronavirus 2 (SARS-CoV-2) and CD147, making meplazumab a promising candidate drug for COVID-19. In this study, biodistribution and dosimetry of [SUP]131[/SUP]I-labeled meplazumab were performed to further evaluate its potential as a therapeutic drug for COVID-19. [SUP]131[/SUP]I-meplazumab was both safe and tolerant in mice and healthy volunteers. A biodistribution study was performed in normal mice, and blood samples were used for pharmacokinetic analysis. Three healthy volunteers were included and subjected to single-photon-emission computed tomography (SPECT) imaging of [SUP]131[/SUP]I-meplazumab within 2 weeks. The distribution in mice and humans was consistent with the in vivo distribution of CD147. Biodistribution and SPECT imaging results exhibited that the liver was the organ with the highest uptake for both mice and humans. Deiodination of [SUP]131[/SUP]I-meplazumab can be observed in vivo, and taking Lugol's solution can protect the thyroid gland effectively. The pharmacokinetic characteristics of [SUP]131[/SUP]I-meplazumab in mice and humans best fit the two-compartment model. The clearance half-life (T[SUB]1/2[/SUB]β) in mice and humans was 117.4 and 223.5 h, respectively. The results indicated that its pharmacokinetic properties in vivo were ideal. The effective dose calculated from healthy volunteers was 0.811 ± 0.260 mSv·MBq[SUP]-1[/SUP], which was twice the value calculated from mice. It was safe and feasible to perform human clinical imaging experiments using a diagnostic dose of [SUP]131[/SUP]I-meplazumab after thyroid closure by Lugol's solution. This study will provide more experimental basis for advancing the clinical translation of meplazumab and will be valuable in evaluating therapeutic interventions for patients with COVID-19, as well as providing a reference for clinical translation studies of other antibody drugs.
Keywords: CD147 receptor; COVID-19; dosimetry; iodine-131; meplazumab.
. 2023 Jan 20.
doi: 10.1021/acs.molpharmaceut.2c00954. Online ahead of print.
Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with [SUP]131[/SUP]I-Labeling and SPECT Imaging
Jiajun Ye[SUP] 1 [/SUP], Weidong Yang[SUP] 1 [/SUP], Zhaojuan Xie[SUP] 1 [/SUP], Yuhao Yan[SUP] 1 [/SUP], Guoquan Li[SUP] 1 [/SUP], Guiyu Li[SUP] 1 [/SUP], Xiang Li[SUP] 1 [/SUP], Wenhui Ma[SUP] 1 [/SUP], Fei Kang[SUP] 1 [/SUP], Mingru Zhang[SUP] 1 [/SUP], Jing Wang[SUP] 1 [/SUP]
Affiliations
- PMID: 36668905
- DOI: 10.1021/acs.molpharmaceut.2c00954
Abstract
Coronavirus disease 2019 (COVID-19) is a serious threat to public health and is in urgent need of specific drugs. Meplazumab, a humanized monoclonal antibody targeting CD147, was confirmed to competitively block the binding between the spike of syndrome coronavirus 2 (SARS-CoV-2) and CD147, making meplazumab a promising candidate drug for COVID-19. In this study, biodistribution and dosimetry of [SUP]131[/SUP]I-labeled meplazumab were performed to further evaluate its potential as a therapeutic drug for COVID-19. [SUP]131[/SUP]I-meplazumab was both safe and tolerant in mice and healthy volunteers. A biodistribution study was performed in normal mice, and blood samples were used for pharmacokinetic analysis. Three healthy volunteers were included and subjected to single-photon-emission computed tomography (SPECT) imaging of [SUP]131[/SUP]I-meplazumab within 2 weeks. The distribution in mice and humans was consistent with the in vivo distribution of CD147. Biodistribution and SPECT imaging results exhibited that the liver was the organ with the highest uptake for both mice and humans. Deiodination of [SUP]131[/SUP]I-meplazumab can be observed in vivo, and taking Lugol's solution can protect the thyroid gland effectively. The pharmacokinetic characteristics of [SUP]131[/SUP]I-meplazumab in mice and humans best fit the two-compartment model. The clearance half-life (T[SUB]1/2[/SUB]β) in mice and humans was 117.4 and 223.5 h, respectively. The results indicated that its pharmacokinetic properties in vivo were ideal. The effective dose calculated from healthy volunteers was 0.811 ± 0.260 mSv·MBq[SUP]-1[/SUP], which was twice the value calculated from mice. It was safe and feasible to perform human clinical imaging experiments using a diagnostic dose of [SUP]131[/SUP]I-meplazumab after thyroid closure by Lugol's solution. This study will provide more experimental basis for advancing the clinical translation of meplazumab and will be valuable in evaluating therapeutic interventions for patients with COVID-19, as well as providing a reference for clinical translation studies of other antibody drugs.
Keywords: CD147 receptor; COVID-19; dosimetry; iodine-131; meplazumab.