Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with 131I-Labeling and SPECT Imaging
Safety, Biodistribution, and Dosimetry Study of Meplazumab, a Potential COVID-19 Therapeutic Drug, with 131I-Labeling and SPECT Imaging
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DOI：
10.1021/acs.molpharmaceut.2c00954
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发表时间：
2023-01-20
影响因子：
4.9
通讯作者：
Wang，Jing
中科院分区：
文献类型：
--
作者：
Ye，Jiajun;Yang，Weidong;Wang，Jing
2019冠状病毒病（COVID-19）是对公共卫生的严重威胁，急需特效药。Meplazumab是一种靶向CD 147的人源化单克隆抗体，已被证实可竞争性阻断2型综合征冠状病毒（SARS-CoV-2）与CD 147之间的结合，使Meplazumab成为一种有希望的COVID-19候选药物。在这项研究中，131 I标记的美普珠单抗的生物分布和剂量测定，以进一步评估其作为COVID-19治疗药物的潜力。131 I-美普珠单抗在小鼠和健康志愿者中既安全又耐受。在正常小鼠中进行生物分布研究，并使用血液样品进行药代动力学分析。纳入3名健康志愿者，并在2周内接受131 I-美普珠单抗单光子发射计算机断层扫描（SPECT）成像。在小鼠和人中的分布与CD 147的体内分布一致。生物分布和SPECT成像结果表明，肝脏是小鼠和人类摄取最高的器官。131 I-meplazumab体内脱碘后，服用Lugol液可有效保护甲状腺。131 I-美普珠单抗在小鼠和人体中的药代动力学特征最符合二室模型。小鼠和人体的清除半衰期（T1/2β）分别为117.4和223.5 h。结果表明，其药代动力学性质较理想。健康志愿者的有效剂量为0.811 ± 0.260 mSv·MBq-1，是小鼠的2倍。在用Lugol溶液闭合甲状腺后，使用诊断剂量的131 I-美普珠单抗进行人体临床成像实验是安全可行的。该研究将为推进美普珠单抗的临床转化提供更多的实验依据，对评估COVID-19患者的治疗干预措施具有重要价值，并为其他抗体药物的临床转化研究提供参考。
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 of131I-labeled meplazumab were performed to further evaluate its potential as a therapeutic drug for COVID-19.131I-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 of131I-meplazumab within 2 weeks. The distribution in mice and humans was consistent with thein vivodistribution of CD147. Biodistribution and SPECT imaging results exhibited that the liver was the organ with the highest uptake for both mice and humans. Deiodination of131I-meplazumab can be observedin vivo, and taking Lugol’s solution can protect the thyroid gland effectively. The pharmacokinetic characteristics of131I-meplazumab in mice and humans best fit the two-compartment model. The clearance half-life (T1/2β) in mice and humans was 117.4 and 223.5 h, respectively. The results indicated that its pharmacokinetic propertiesin vivowere ideal. The effective dose calculated from healthy volunteers was 0.811 ± 0.260 mSv·MBq–1, which was twice the value calculated from mice. It was safe and feasible to perform human clinical imaging experiments using a diagnostic dose of131I-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.