Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST-NIRS), Inage, Chiba 263-8555, Japan.
International Center for Cell and Gene Therapy, Fujita Health University, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
Int J Mol Sci. 2020 Mar 26;21(7):2304. doi: 10.3390/ijms21072304.
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-labeled antibody 067-213, which has high affinity for human CD73, to act as a noninvasive imaging probe.
Cell binding and competitive inhibition assays for In-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.
In-labeled 067-213 bound to MIAPaCa-2 and A431 cells in a CD73-dependent manner and the affinity loss after In-labeling was limited. Biodistribution and SPECT/CT studies with In-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.
In-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.
CD73 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发挥重要作用。CD73 靶向治疗的疗效取决于 CD73 的表达水平；因此，监测癌症患者的 CD73 状态可为选择受益于 CD73 靶向治疗的患者提供有价值的信息。在这里，我们评估了高亲和力结合人 CD73 的 In 标记抗体 067-213 作为一种非侵入性成像探针的能力。
使用 MIAPaCa-2（高 CD73 表达）和 A431（低 CD73 表达）细胞进行 In 标记的 067-213 的细胞结合和竞争性抑制测定。进行体内评估，在 MIAPaCa-2 和 A431 荷瘤小鼠中进行生物分布和 SPECT/CT 研究。为了估算人类的吸收剂量，在健康大鼠中进行了生物分布和 SPECT/CT 研究。
In 标记的 067-213 以 CD73 依赖性方式结合 MIAPaCa-2 和 A431 细胞，并且 In 标记后的亲和力损失有限。在小鼠中进行的 In 标记的 067-213 的生物分布和 SPECT/CT 研究显示，MIAPaCa-2 肿瘤中摄取量高，A431 肿瘤中摄取量低。在大鼠中，该探针在包括内源性 CD73 表达器官在内的正常器官中没有高摄取。估计的人类吸收剂量相当低。
In 标记的 067-213 显示出 CD73 表达依赖性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 有望成为一种成像探针，用于非侵入性评估患者的 CD73 表达水平。我们的数据鼓励进一步的临床研究，以阐明 CD73 监测在接受 CD73 靶向免疫治疗的患者中的作用。
