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Implantation and Monitoring by PET/CT of an Orthotopic Model of Human Pleural Mesothelioma in Athymic Mice
Published on: December 21, 2019
Immuno-PET imaging of mesothelin in ovarian cancer with 68Ga-XH04: a first-in-human study
Yueling Deng1,2,3, Xiao Zhang1,2,3, Zhidi Pan4
1Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, Hubei Province, 430022, China.
Background:
Mesothelin is highly expressed in ovarian cancer and represents a promising target for precision imaging and therapy. This study aimed to develop and evaluate ⁶⁸Ga-XH04, a novel mesothelin-targeted immuno-PET tracer for non-invasive imaging of mesothelin expression in preclinical models and patients.
Methods:
XH04, a high-affinity anti-mesothelin antigen-binding fragment (Fab), was engineered and conjugated with NOTA for radiolabeling with ⁶⁸Ga. Binding affinity and specificity were assessed in vitro using cell lines with graded mesothelin expression. In vivo PET imaging, biodistribution, and pharmacokinetics were evaluated in xenograft models. Immunohistochemistry was performed to correlate tracer uptake with mesothelin levels. A first-in-human pilot study was conducted in a healthy volunteer and ovarian cancer patients to assess safety, imaging characteristics, and descriptive comparison with ¹⁸F-FDG PET/CT.
Results:
⁶⁸Ga-XH04 exhibited high radiochemical purity (> 98%) and nanomolar affinity for mesothelin. In preclinical models, ⁶⁸Ga-XH04 showed rapid clearance and higher uptake in mesothelin-high xenografts than in mesothelin-low xenografts, supporting exploratory assessment of mesothelin-dependent tracer accumulation. Immunohistochemistry confirmed the correlation between tracer uptake and mesothelin expression. In patients, ⁶⁸Ga-XH04 was well tolerated and visualized primary and metastatic lesions. In this preliminary cohort, ⁶⁸Ga-XH04 provided information complementary to ¹⁸F-FDG PET/CT and identified lesions with relatively low FDG uptake.
Conclusion:
⁶⁸Ga-XH04 demonstrated the feasibility of specific, noninvasive, and high-contrast imaging of mesothelin expression in ovarian cancer with favorable pharmacokinetics. This tracer may complement existing imaging modalities by enabling noninvasive assessment of mesothelin expression and may provide imaging-based information to support future investigation of mesothelin-targeted therapies. Larger prospective studies are required to validate its diagnostic value and clinical utility.
Trial Registration:
ClinicalTrials.gov (NCT06843629); registered on December 20, 2024.
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