Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression
Radiolabeled Human Monoclonal Antibody 067-213 has the Potential for Noninvasive Quantification of CD73 Expression
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DOI：
10.3390/ijms21072304
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发表时间：
2020-04-01
影响因子：
5.6
通讯作者：
Higashi, Tatsuya
中科院分区：
文献类型：
--
作者：
Sudo, Hitomi;Tsuji, Atsushi B.;Higashi, Tatsuya
背景资料：CD 73是一种调节细胞外腺苷浓度的外核苷酸酶，在腺苷介导的免疫抑制途径中起重要作用。CD 73靶向治疗的疗效取决于CD 73的表达水平;因此，监测癌症患者的CD 73状态将为选择将从CD 73靶向治疗中获益的患者提供有用的信息。在这里，我们评估了In-111标记的抗体067-213作为非侵入性成像探针的能力，该抗体对人CD 73具有高亲和力。研究方法：使用MIAPaCa-2（高CD 73表达）和A431（低CD 73表达）细胞进行In-111标记的067-213的细胞结合和竞争性抑制试验。对于体内评估，在MIAPaCa-2和A431荷瘤小鼠中进行了生物分布和SPECT/CT研究。为了估计人体吸收剂量，在健康大鼠中进行了生物分布和SPECT/CT研究。结果：In-111标记的067-213与MIAPaCa-2和A431细胞以CD 73依赖的方式结合，In-111标记后亲和力损失有限。In-111标记的067-213在小鼠中的生物分布和SPECT/CT研究显示在MIAPaCa-2肿瘤中的高摄取和在A431肿瘤中的较低摄取。在大鼠中，探针在正常器官中没有显示出高摄取，包括内源性CD 73表达器官。估计的人体吸收剂量相当低。结论：In-111标记的067-213显示出CD 73表达依赖的肿瘤摄取和正常器官和组织中的低摄取。放射性标记的067-213有望作为一种成像探针，用于无创评估患者的CD 73表达水平。我们的数据鼓励进一步的临床研究，以阐明CD 73监测在接受CD 73靶向免疫治疗的患者中的作用。
Background: CD73 is an ectonucleotidase regulating extracellular adenosine concentration and plays an important role in adenosine-mediated immunosuppressive pathways. The efficacy of CD73-targeted therapy depends on the expression levels of CD73; therefore, monitoring CD73 status in cancer patients would provide helpful information for selection of patients who would benefit from CD73-targeted therapy. Here, we evaluated the ability of In-111-labeled antibody 067-213, which has high affinity for human CD73, to act as a noninvasive imaging probe. Methods: Cell binding and competitive inhibition assays for In-111-labeled 067-213 were conducted using MIAPaCa-2 (high CD73 expression) and A431 (low CD73 expression) cells. For in vivo assessments, biodistribution and SPECT/CT studies were conducted in MIAPaCa-2 and A431 tumor-bearing mice. To estimate the absorbed dose in humans, biodistribution and SPECT/CT studies were conducted in healthy rats. Results: In-111-labeled 067-213 bound to MIAPaCa-2 and A431 cells in a CD73-dependent manner and the affinity loss after In-111-labeling was limited. Biodistribution and SPECT/CT studies with In-111-labeled 067-213 in mice showed high uptake in MIAPaCa-2 tumors and lower uptake in A431 tumors. In rats, the probe did not show high uptake in normal organs, including endogenously CD73-expressing organs. The estimated absorbed doses in humans were reasonably low. Conclusions: In-111-labeled 067-213 showed CD73-expression-dependent tumor uptake and low uptake in normal organs and tissues. Radiolabeled 067-213 holds promise as an imaging probe for noninvasive evaluation of CD73 expression levels in patients. Our data encourage further clinical studies to clarify a role for CD73 monitoring in patients receiving CD73-targeted immune therapy.