Detection and viability of murine NK cells in vivo in a lymphoma model using fluorine-19 MRI,NMR in Biomedicine

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Detection and viability of murine NK cells in vivo in a lymphoma model using fluorine-19 MRI
NMR in Biomedicine ( IF 2.7 ) Pub Date : 2021-08-18 , DOI: 10.1002/nbm.4600
Lawrence M Lechuga ₁ , Matthew H Forsberg ₂ , Kirsti L Walker _{2,

3} , Kai D Ludwig ₁ , Christian M Capitini _{2,

4,

5} , Sean B Fain _{1,

4,

5,

6}

Affiliation

Natural killer (NK) cell therapies are being increasingly used as an adoptive cell therapy for cancer because they can recognize tumor cells in an antigen-independent manner. While promising, the understanding of NK cell persistence, particularly within a harsh tumor microenvironment, is limited. Fluorine-19 (¹⁹F) MRI is a noninvasive imaging modality that has shown promise in longitudinally tracking cell populations in vivo; however, it has not been studied on murine NK cells. In this study, the impact of ¹⁹F labeling on murine NK cell viability and function was assessed in vitro and then used to quantify NK cell persistence in vivo. While there was no noticeable impact on viability, labeling NK cells with ¹⁹F did attenuate cytotoxicity against lymphoma cells in vitro. Fluorescent microscopy verified ¹⁹F labeling in both the cytoplasm and nucleus of NK cells. Lymphoma-bearing mice were given intratumoral injections of ¹⁹F-labeled NK cells in which signal was detectable across the 6 day observation period via ¹⁹F MRI. Quantification from the composite images detected 78-94% of the initially injected NK cells across 6 days, with a significant decrease between Days 3 and 6. Postmortem flow cytometry demonstrated retention of ¹⁹F intracellularly within adoptively transferred NK cells with less than 1% of ¹⁹F-containing cells identified as tumor-associated macrophages that presumably ingested nonviable NK cells. This work demonstrates that ¹⁹F MRI offers a specific imaging platform to track and quantify murine NK cells within tumors noninvasively.

中文翻译：

使用 fluorine-19 MRI 检测淋巴瘤模型中小鼠 NK 细胞的体内活性

自然杀伤 (NK) 细胞疗法越来越多地用作癌症的过继细胞疗法，因为它们可以以抗原非依赖性方式识别肿瘤细胞。虽然很有前途，但对 NK 细胞持久性的理解，尤其是在恶劣的肿瘤微环境中，是有限的。Fluorine-19 ( ¹⁹ F) MRI 是一种非侵入性成像方式，在纵向追踪体内细胞群方面显示出前景；然而，尚未对小鼠 NK 细胞进行研究。在这项研究中，在体外评估了¹⁹ F 标记对小鼠 NK 细胞活力和功能的影响，然后用于量化 NK 细胞在体内的持久性。虽然对生存能力没有明显影响，但用^{19标记 NK 细胞}F 确实在体外减弱了对淋巴瘤细胞的细胞毒性。荧光显微镜证实了 NK 细胞细胞质和细胞核中的¹⁹ F 标记。对携带淋巴瘤的小鼠进行瘤内注射¹⁹ F 标记的 NK 细胞，其中通过¹⁹ F MRI 在 6 天的观察期内可检测到信号。合成图像的量化在 6 天内检测到 78-94% 的最初注射的 NK 细胞，在第 3 天和第 6 天之间显着下降。死后流式细胞术显示¹⁹ F 在过继转移的 NK 细胞内保留在细胞内，不到 1% ¹⁹含 F 的细胞被鉴定为肿瘤相关巨噬细胞，可能摄取了无法存活的 NK 细胞。这项工作表明¹⁹ F MRI 提供了一个特定的成像平台，可以无创地跟踪和量化肿瘤内的小鼠 NK 细胞。

更新日期：2021-08-18

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