Molecular imaging of tumors with nanobodies and antibodies: Timing and dosage are crucial factors for improved in vivo detection
Molecular imaging of tumors with nanobodies and antibodies: Timing and dosage are crucial factors for improved in vivo detection
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DOI：
10.1002/cmmi.1637
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发表时间：
2015-09-01
影响因子：
--
通讯作者：
Koch-Nolte, Friedrich
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文献类型：
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作者：
Bannas, Peter;Lenz, Alexander;Koch-Nolte, Friedrich
用于体内成像的纳米抗体和常规抗体的效用是众所周知的，但是一种相对于另一种的最佳给药和定时方案尚未建立。我们的目的是提高特异性肿瘤成像在体内与纳米抗体和常规抗体使用近红外荧光（NIRF）成像。我们使用在淋巴瘤细胞上表达的ARTC 2作为模型靶抗原。ARTC 2特异性纳米抗体s +16 a和常规抗体Nika 102用NIRF染料AF 680标记。在注射5、10、25或50 μ g每种缀合物后24小时内进行ARTC 2阳性和ARTC 2阴性异种移植物的体内NIRF成像。通过离体NIRF成像、流式细胞术和荧光显微镜验证特异性靶结合和组织渗透。体内s +16 a（680）的近红外成像显示肿瘤积聚比Nika 102（680）快6倍。使用50 μ g s +16 a（680）增加了ARTC 2阳性肿瘤的特异性信号，而不增加背景信号，使肿瘤与背景（T/B）的比率在注射后6小时内为12.4 +/- 4.2。50微克Nika 102（680）增加了ARTC 2阳性肿瘤的特异性信号，但也增加了ARTC 2阴性肿瘤和背景的特异性信号，从而将T/B比限制在6.1 +/- 2.0。10微克Nika 102（680）仅略微降低了特定肿瘤信号，但显著降低了背景信号。离体分析证实s +16 a的肿瘤渗透更快更深（680）。使用纳米抗体s +16 a允许具有高T/B比率的当天成像，而抗体Nika 102仅在注射后24小时给出最佳成像结果。纳米抗体s +16 a需要高剂量，而抗体Nika 102在低剂量下具有最佳的T/B比。因此，在比较用于分子成像目的的纳米抗体和常规抗体时，应解决时机和剂量问题。版权所有（C）2015约翰威利父子有限公司
The utility of nanobodies and conventional antibodies for in vivo imaging is well known, but optimum dosing and timing schedules for one versus the other have not been established. We aimed to improve specific tumor imaging in vivo with nanobodies and conventional antibodies using near-infrared fluorescence (NIRF) imaging. We used ARTC2 expressed on lymphoma cells as a model target antigen. ARTC2-specific nanobody s + 16a and conventional antibody Nika102 were labeled with NIRF-dye AF680. In vivo NIRF-imaging of ARTC2-positive and ARTC2-negative xenografts was performed over 24h post-injection of 5, 10, 25, or 50 mu g of each conjugate. Specific target-binding and tissue-penetration were verified by NIRF imaging ex vivo, flow cytometry and fluorescence microscopy. NIRF-imaging of s + 16a(680)in vivo revealed a six times faster tumor accumulation than of Nika102(680). Using 50 mu g of s + 16a(680) increased the specific signals of ARTC2-positive tumors without increasing background signals, allowing a tumor-to-background (T/B) ratio of 12.4 +/- 4.2 within 6h post-injection. Fifty micrograms of Nika102(680) increased specific signals of ARTC2-positive tumors but also of ARTC2-negative tumors and background, thereby limiting the T/B ratio to 6.1 +/- 2.0. Ten micrograms of Nika102(680) only slightly reduced specific tumor signals but dramatically reduced background signals. Ex vivo analyses confirmed a faster and deeper tumor penetration with s + 16a(680). Using nanobody s + 16a allowed same-day imaging with a high T/B ratio, whereas antibody Nika102 gave optimal imaging results only 24h post injection. Nanobody s + 16a required a high dose, whereas antibody Nika102 had the best T/B-ratio at a low dose. Therefore, timing and dosage should be addressed when comparing nanobodies and conventional antibodies for molecular imaging purposes. Copyright (C) 2015 John Wiley & Sons, Ltd.