99mTc-CD3813: A Nanobody-Based Single Photon Emission Computed Tomography Radiotracer with Clinical Potential for Myeloma Imaging and Evaluation of CD38 Expression
99mTc-CD3813: A Nanobody-Based Single Photon Emission Computed Tomography Radiotracer with Clinical Potential for Myeloma Imaging and Evaluation of CD38 Expression
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99mTc-CD3813：一种基于纳米抗体的单光子发射计算机断层扫描放射性示踪剂，具有用于骨髓瘤成像和 CD38 表达评估的临床潜力
DOI：
10.1021/acs.molpharmaceut.2c00279
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发表时间：
2022
影响因子：
4.9
通讯作者：
Fan Wang
中科院分区：
文献类型：
--
作者：
Linqing Shi;Bo Chen;Tianyu Liu;Liqiang Li;Biao Hu;Chenzhen Li;Bing Jia;Fan Wang
Daratumumab (DARA) 是一种抗 CD38 单克隆抗体，用于治疗多发性骨髓瘤 (MM)。肿瘤CD38表达水平是决定DARA治疗疗效的重要因素之一。因此，临床迫切需要一种无创工具来评估癌症患者在DARA治疗之前、期间和之后的CD38水平。在本研究中，我们制备了一种新的分子成像探针99mTc-CD3813，即99mTc标记的纳米抗体CD3813，用于通过单光子发射计算机断层扫描（SPECT）对CD38表达进行无创成像。我们评估了 99mTc-CD3813 的 CD38 亲和力和特异性以及其在 MM 和淋巴瘤异种移植模型中对 CD38 表达进行成像的能力。99mTc-CD3813 SPECT/CT 能够可视化动物模型中的皮下/原位骨髓瘤病变，并且比 18 F-氟脱氧葡萄糖 (18 F-FDG) 正电子发射断层扫描具有优势。过量的 DARA 对其肿瘤摄取的影响较小（3.14 ± 0.83 vs 2.29 ± 0.91 %ID/g，n.s.），强烈表明 99mTc-CD3813 和 DARA 在与 CD38 的结合方面不存在竞争。99mTc-CD3813 SPECT/CT 显示在 DARA 治疗下 Ramos 小鼠的 CD38 表达显着降低。通过减少肿瘤摄取（3.04 ± 0.70 vs 1.07 ± 0.28 %ID/cc，P< 0.001）。99mTc-CD3813 SPECT/CT 还能够检测到由于 CD38 上调而导致的肿瘤摄取增加（0.79 ± 0.29 vs 2.12 ± 0.12 %ID/cc，P< 0.001） 99mTc-CD3813 是一种很有前途的 SPECT 放射性示踪剂，用于对 CD38 阳性肿瘤进行成像，并且具有作为分子成像工具的临床潜力，用于评估 DARA 治疗之前、期间和之后患者的 CD38 表达水平。
Daratumumab (DARA) is an anti-CD38 monoclonal antibody for the treatment of multiple myeloma (MM). The tumor CD38 expression level is one of the important factors in determining the efficacy of DARA treatment. Therefore, there is an urgent clinical need for a noninvasive tool to evaluate the CD38 levels in cancer patients before, during, and after DARA treatment. In this study, we prepared a new molecular imaging probe99mTc-CD3813, the99mTc-labeled nanobody CD3813, for noninvasive imaging of CD38 expression by single photon emission computed tomography (SPECT). We evaluated99mTc-CD3813 for its CD38 affinity and specificity and its capacity to image the CD38 expression in the MM and lymphoma xenografts models.99mTc-CD3813 SPECT/CT is able to visualize subcutaneous/orthotopic myeloma lesions in animal models and has advantages over18F-fluorodeoxyglucose (18F-FDG) positron emission tomography. Excess DARA has less impact on its tumor uptake (3.14 ± 0.83 vs 2.29 ± 0.91 %ID/g, n.s.), strongly suggesting that there is no competition between99mTc-CD3813 and DARA in binding to CD38.99mTc-CD3813 SPECT/CT revealed significant reduction in CD38 expression in the Ramos-bearing mice under DARA treatment, as evidenced by their reduced tumor uptake (3.04 ± 0.70 vs 1.07 ± 0.28 %ID/cc,P< 0.001).99mTc-CD3813 SPECT/CT was also able to detect the increased tumor uptake (0.79 ± 0.29 vs 2.12 ± 0.12 %ID/cc,P< 0.001) due to the upregulation of CD38 levels caused by all-trans retinoic acid infection.99mTc-CD3813 is a promising SPECT radiotracer for imaging the CD38-positive tumors and has clinical potential as a molecular imaging tool for evaluation of the CD38 expression level in patients before, during, and after DARA treatment.