Purpose

A noninvasive method for evaluating the infiltration of CD8⁺ T cells in tumors is urgently needed to monitor the response to immunotherapy. This study investigated the performance of a [⁶⁸Ga]Ga-NODAGA-SNA006 in positron emission tomography (PET) imaging of CD8⁺ T cells in patients with solid malignancies.

Methods

This human dose-escalation PET imaging study involved eleven patients (lung cancer, 8; gastric carcinoma, 1; esophageal carcinoma, 2). Approximately 150 MBq of [⁶⁸Ga]Ga-NODAGA-SNA006 with varying nanobody masses (100 µg, 300 µg, 500 µg, 800 µg) was administered, and PET/computed tomography (CT) scans were performed at 15–30, 60–90 and 120 min postinjection (p.i.). Data regarding biodistribution, pharmacokinetics and radiation dosimetry were evaluated. CD8⁺ T-cell infiltration in biopsy samples was also measured via immunohistochemistry (IHC) for correlation analysis with the tumor uptake of [⁶⁸Ga]Ga-NODAGA-SNA006 PET.

Results

[⁶⁸Ga]Ga-NODAGA-SNA006 was well tolerated by all eleven subjects. The highest radioactive uptake was observed in the spleen, followed by the kidneys and bladder. Liver uptake decreased with increasing nanobody mass. Rapid clearance (t_1/2<30 min) of [⁶⁸Ga]Ga-NODAGA-SNA006 from whole blood and serum was observed. Furthermore, ⁶⁸Ga uptake in tumors (SUVmean) exhibited a linear relationship with CD8⁺ T-cell infiltration in biopsy samples (R² = 0.757, p = 0.011), suggesting that the tumor uptake of [⁶⁸Ga]Ga-NODAGA-SNA006 may represent the degree of CD8⁺ T-cell infiltration in the tumor.

Conclusion

The use of [⁶⁸Ga]Ga-NODAGA-SNA006 is safe, feasible, and well tolerated. [⁶⁸Ga]Ga-NONAGA-SNA006 PET imaging can accurately detect CD8 expression inside tumors with favorable pharmacokinetics, thus providing a feasible method for noninvasive quantitative assessment of CD8⁺ T-cell tumor infiltration and monitoring the response to immunotherapy.

Trial Registration

NCT05126927 (19 November 2021, retrospectively registered).

中文翻译：

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[68Ga]Ga -NODAGA-SNA006 实体恶性肿瘤中 PET 成像 CD8+ T 细胞浸润的人体剂量递增研究

 目的

迫切需要一种评估肿瘤中 CD8⁺ T 细胞浸润的无创方法来监测对免疫治疗的反应。本研究调查了 [⁶⁸Ga]Ga-NODAGA-SNA006 在实体恶性肿瘤患者 CD8⁺ T 细胞正电子发射断层扫描 （PET） 成像中的性能。

 方法

这项人体剂量递增 PET 成像研究涉及 11 名患者（肺癌 8 例;胃癌 1 例;食管癌 2 例）。施用大约 150 MBq 具有不同纳米抗体质量（100 μg、300 μg、500 μg、800 μg）的 [⁶⁸Ga]Ga-NODAGA-SNA006，并在注射后 15-30、60-90 和 120 分钟 （pi） 进行 PET/计算机断层扫描 （CT） 扫描。评估了有关生物分布、药代动力学和放射剂量测定的数据。还通过免疫组织化学 （IHC） 测量活检样本中 CD8⁺ T 细胞浸润，以分析 [⁶⁸Ga]Ga-NODAGA-SNA006 PET 的肿瘤摄取。

 结果

[⁶⁸加]Ga-NODAGA-SNA006 被所有 11 例受试者耐受良好。在脾脏中观察到的放射性吸收最高，其次是肾脏和膀胱。肝脏摄取随着纳米抗体质量的增加而降低。观察到全血和血清中 [⁶⁸Ga]Ga-NODAGA-SNA006 的快速清除 （t_1/2<30 min）。此外，^{肿瘤中 68}Ga 的摄取 （SUVmean） 与活检样本中 CD8⁺ T 细胞浸润呈线性关系 （R² = 0.757，p = 0.011）， 表明肿瘤对 [⁶⁸Ga]Ga-NODAGA-SNA006 的摄取可能代表肿瘤中 CD8 ⁺ T 细胞浸润的程度。

 结论

[⁶⁸Ga]Ga-NODAGA-SNA006 的使用是安全、可行的且耐受性良好的。[⁶⁸加]Ga-NONAGA-SNA006 PET 成像可以准确检测肿瘤内部的 CD8 表达，具有良好的药代动力学，从而为无创定量评估 CD8⁺ T 细胞肿瘤浸润和监测免疫治疗的反应提供了一种可行的方法。

 试用注册

NCT05126927（2021 年 11 月 19 日，回顾性注册）。