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 Ga-NODAGA-SNA006 for instant PET (iPET) imaging of CD8 T cells.
Methods: A novel nanobody without a hexahistidine (His) tag, SNA006-GSC, was designed, site-specifically conjugated with NODAGA-maleimide and radiolabelled with Ga. The PET imaging profiles of 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 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: Ga-NODAGA-SNA006 was prepared with RCP > 98% and SA > 100 GBq/μmol. 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 (t < 20 min). A preliminary quantitative linear relationship (R = 0.9668, p < 0.0001 for xenografts and R = 0.7924, p = 0.0013 for lung patients) appeared between Ga-NODAGA-SNA006 uptake and CD8 expression. Ga-NODAGA-SNA006 was well tolerated by all patients.
Conclusion: 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).
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