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Updated: Jan 12, 2026
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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
First-in-human study of a novel bifunctional PET tracer [68Ga]Ga-DOTA-NI-FAPI-04 targeting FAP and hypoxia
Jie Zang1,2, Hongfei Cheng1,2, Yang Luo3
1Department of Nuclear Medicine, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fujian Province, Fuzhou, 350212, China.
Purpose:
Preclinical studies have demonstrated that [68Ga]Ga/[177Lu]Lu-DOTA-NI-FAPI-04, a bivalent agent containing an extra hypoxia-sensitive 2-nitroimidazole (NI) group, exhibited favorable tumor binding affinity and improved tumor uptake and retention than [68Ga]Ga/[177Lu]Lu-DOTA-FAPI-04. This study aims to further investigate the value of clinical application for [68Ga]Ga-DOTA-NI-FAPI-04 PET/CT via a direct head-to-head comparison with [68Ga]Ga-DOTA-FAPI-04.
Methods:
A total of 50 patients underwent paired [68Ga]Ga-DOTA-NI-FAPI-04 and [68Ga]Ga-DOTA-FAPI-04 PET/CT within 1 week interval. Among these, four patients underwent serial dynamic [68Ga]Ga-DOTA-NI-FAPI-04 PET scans for dosimetry evaluation, and the others underwent scans at 60 min and 120 min. Additionally, we calculated the SUVmax differences (ΔSUVmax) by [68Ga]Ga-DOTA-NI-FAPI-04 minus [68Ga]Ga-DOTA-FAPI-04 PET/CT for further analysis. Immunohistochemistry for FAP and hypoxia-inducible factor-1 alpha (HIF-1α) was performed in 22 primary tumors.
Results:
The effective absorbed dose of [68Ga]Ga-DOTA-NI-FAPI-04 PET/CT was calculated as 1.95E-02 mSv/MBq. Tumor uptake of [68Ga]Ga-DOTA-NI-FAPI-04 showed rapid uptake and steady values (average SUVmax 11.6-13.0 from 3 to 120 min). [68Ga]Ga-DOTA-NI-FAPI-04 exhibited significantly higher uptake in tumor lesions compared to [68Ga]Ga-DOTA-FAPI-04 PET/CT, particularly in primary tumors (P < 0.05), nodal metastases (P < 0.001), bone metastases (P < 0.001), and liver metastases (P < 0.05). That of FAP expression was correlated with that of HIF-1α (r = 0.661, P < 0.001), and the expression of HIF-1α showed a positive correlation with ΔSUVmax (r = 0.528, P = 0.011).
Conclusion:
[68Ga]Ga-DOTA-NI-FAPI-04 showed significantly higher tumor uptake and retention over [68Ga]Ga-DOTA-FAPI-04, with particularly enhanced visualization of hypoxic lesions, suggesting that hypoxia-sensitive moiety may play an important role in detection of tumors. Further study of [177Lu]Lu-DOTA-NI-FAPI-04 in humans is warranted to explore its clinical applications. URL OF REGISTRY: https://clinicaltrials.gov/study/NCT06688305 .
Trial Registration:
ClinicalTrials.gov, NCT06688305, Registered 14 November 2024, retrospectively registered.
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