Human dose-escalation study of PET imaging CD8+ T-cell infiltration in solid malignancies with [68Ga]Ga -NODAGA-SNA006.
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 soli...
| Published in: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 52; no. 4; pp. 1332 - 1345 |
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| Main Authors: | , , , , , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Published: |
Springer Nature
Mar2025
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=183131169&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 183131169 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Mar2025 vid: 52 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 183131169 181511473 10.1007/s00259-024-06999-x 183131169 ppf: 1332 ppct: 13 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Human dose-escalation study of PET imaging CD8+ T-cell infiltration in solid malignancies with [68Ga]Ga -NODAGA-SNA006. aug: au: Wang, Yan Zheng, Meng Zhao, Jun Wang, Chao Zhao, Shandong Bian, Yicong Dai, Na Zheng, Yushuang Sang, Shibiao Guo, Linchuan Huang, Chenrong Zhang, Hua Jiang, Jiwei Xu, Chun Zhao, Qi Han, Jiajun Xu, Tao Qin, Songbing Miao, Liyan affil: https://ror.org/051jg5p78 Department of Clinical Pharmacology, First Affiliated Hospital of Soochow University, Suzhou, China sug: ab: 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 (t1/2<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). pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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