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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 13/2022

13-07-2022 | Positron Emission Tomography | Original Article

Pilot study of a novel nanobody 68 Ga-NODAGA-SNA006 for instant PET imaging of CD8+ T cells

Authors: Yan Wang, Chao Wang, Minzhou Huang, Songbing Qin, Jun Zhao, Shibiao Sang, Meng Zheng, Yicong Bian, Chenrong Huang, Hua Zhang, Lingchuan Guo, Jiwei Jiang, Chun Xu, Na Dai, Yushuang Zheng, Jiajun Han, Min Yang, Tao Xu, Liyan Miao

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 13/2022

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Abstract

Purpose

Positron emission tomography (PET) with specific diagnostic probes for quantifying CD8+ T cells has emerged as a powerful technique for monitoring the immune response. However, most CD8+ T cell radiotracers are based on antibodies or antibody fragments, which are slowly cleared from circulation. Herein, we aimed to develop and assess 68 Ga-NODAGA-SNA006 for instant PET (iPET) imaging of CD8+ T cells.

Methods

A novel nanobody without a hexahistidine (His6) tag, SNA006-GSC, was designed, site-specifically conjugated with NODAGA-maleimide and radiolabelled with 68 Ga. The PET imaging profiles of 68 Ga-NODAGA-SNA006 were evaluated in BALB/c MC38-CD8+/CD8− tumour models and cynomolgus monkeys. Three volunteers with lung cancer underwent whole-body PET/CT imaging after 68 Ga-NODAGA-SNA006 administration. The biodistribution, pharmacokinetics and dosimetry of patients were also investigated. In addition, combined with immunohistochemistry (IHC), the quantitative performance of the tracer for monitoring CD8 expression was evaluated in BALB/c MC38-CD8+/CD8− and human subjects.

Results

68 Ga-NODAGA-SNA006 was prepared with RCP > 98% and SA > 100 GBq/μmol. 68 Ga-NODAGA-SNA006 exhibited specific uptake in MC38-CD8+ xenografts tumours, CD8-rich tissues (such as the spleen) in monkeys and CD8+ tumour lesions in patients within 1 h. Fast washout from circulation was observed in three volunteers (t1/2 < 20 min). A preliminary quantitative linear relationship (R2 = 0.9668, p < 0.0001 for xenografts and R2 = 0.7924, p = 0.0013 for lung patients) appeared between 68 Ga-NODAGA-SNA006 uptake and CD8 expression. 68 Ga-NODAGA-SNA006 was well tolerated by all patients.

Conclusion

68 Ga-NODAGA-SNA006 PET imaging can instantly quantify CD8 expression with an ideal safety profile and is expected to be important for dynamically tracking CD8+ T cells and monitoring immune responses for individualised cancer immunotherapy.

Trial registration

NCT05126927 (19 November 2021, retrospectively registered).
Appendix
Available only for authorised users
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Metadata
Title
Pilot study of a novel nanobody 68 Ga-NODAGA-SNA006 for instant PET imaging of CD8+ T cells
Authors
Yan Wang
Chao Wang
Minzhou Huang
Songbing Qin
Jun Zhao
Shibiao Sang
Meng Zheng
Yicong Bian
Chenrong Huang
Hua Zhang
Lingchuan Guo
Jiwei Jiang
Chun Xu
Na Dai
Yushuang Zheng
Jiajun Han
Min Yang
Tao Xu
Liyan Miao
Publication date
13-07-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 13/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05903-9

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