Abstract 5923: Human dose-escalation study of CD8+T-cell infiltration in solid malignancies with68Ga-NODAGA-SNA006 by PET imaging

Abstract Purpose: A noninvasive method for evaluating the infiltration of CD8+ T cells in tumors is urgently needed for monitoring the response to immunotherapy. This study (NCT05126927) investigated the performance of a 68Ga-NODAGA-SNA006 by positron emission tomography (PET) imaging of CD8+ T cells in patients with solid malignancies. Methods: This human dose-escalation PET imaging study included nine patients (lung cancer, 7; gastric carcinoma, 1; esophageal carcinoma, 1). Approximately 150 MBq of 68Ga-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 min, 60-90 min, 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 by IHC staining for correlation analysis with tumor uptake of 68Ga-NODAGA-SNA006 PET. Results: 68Ga-NODAGA-SNA006 was well tolerated by all nine subjects. The highest radioactive uptake was observed in the spleen, with SUVmax ranging from 60.77 ± 25.05, 66.78±5.64, 70.36±20.94, 56.17 ± 4.69 at 60 min for 100 µg, 300 µg, 500 µg, and 800 µg, respectively, followed by the kidneys and bladder. The SUVmax of kidneys are from 9.20 ± 1.85 to 18.54 ±2.36 for 100 µg to 800 µg. However, the uptake of 68Ga-NODAGA-SNA006 in bladder varied dramatically, depending on the excretion status of patients. Liver uptake decreased with increasing dose of nanobody, maximal (SUVmax: 14.07 ± 2.88) with low nanobody masses (100 µg) and significantly reduced (SUVmax: 6.64 ± 1.30) with high nanobody masses (800 µg). Rapid clearance (t1/2<30 min) of 68Ga-NODAGA-SNA006 from whole blood and serum was observed. Furthermore, the uptake of 68Ga-NODAGA-SNA006 in tumors (SUVmean) exhibited a linear relationship with the CD8+ T-cell infiltration in biopsy samples (R2=0.757, p=0.011), suggesting that the tumor uptake of 68Ga-NODAGA-SNA006 may represent the degree of CD8+ T-cell infiltration in the tumor. Conclusion: The use of 68Ga-NODAGA-SNA006 is safe, feasible, and well tolerated. 68Ga-NONAGA-SNA006 PET imaging can accurately detect CD8+ T cells with favorable pharmacokinetics, thus providing a feasible method for the noninvasive quantitative assessment of CD8+ T-cell infiltration and monitoring of response to immunotherapy. Citation Format: Yan Wang, Meng Zheng, Jun Zhao, Chao Wang, Chunchun Wei, Shandong Zhao, Yicong Bian, Na Dai, Yushuang Zheng, Shibiao sang, Linchuan Guo, Chenrong Huang, Hua Zhang, Jiwei Jiang, Chun Xu, Qi Zhao, Jiajun Han, Tao Xu, Songbing Qin, Liyan Miao. Human dose-escalation study of CD8+T-cell infiltration in solid malignancies with68Ga-NODAGA-SNA006 by PET imaging [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5923.