2. Academic Validation
  3. Design and Preclinical Evaluation of First 68Ga-Labeled Cathepsin D-Targeted Radiotracers

Design and Preclinical Evaluation of First 68Ga-Labeled Cathepsin D-Targeted Radiotracers

  • J Med Chem. 2025 Dec 11;68(23):25143-25156. doi: 10.1021/acs.jmedchem.5c02151.
Yue Xi 1 2 3 4,  Xiangwei Wang 1 2 3 4,  Mengjing Ji 1 2 3 4,  Jianping Zhang 1 2 3 4,  Xiaoping Xu 1 2 3 4,  Simin He 1 2 3 4,  Shaoli Song 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • 2 Center for Biomedical Imaging, Fudan University, Shanghai 200032, China.
  • 3 Shanghai Engineering Research Center of Molecular Imaging Radiotracers, Shanghai 200032, China.
  • 4 Key Laboratory of Nuclear Physics and Ion-beam Application (MOE), Fudan University, Shanghai 200433, China.
PMID: 41296505 DOI: 10.1021/acs.jmedchem.5c02151
Abstract

Cathepsin D (CTSD), a lysosomal aspartic protease linked to Cancer progression and poor patient outcomes, is underexplored as a diagnostic biomarker. This study developed the first CTSD-targeted radiotracers, identifying [68Ga]Ga-NOTA-FZCD-3 as optimal due to its strong binding to CTSD (dissociation constant = 0.65 μM), rapid clearance from the body (elimination half-life = 16.61 min), and high tumor-specific uptake in mouse models. Imaging analysis revealed that tumors with higher CTSD levels absorbed more of the tracer, particularly in the MDA-MB-175VII model, which showed the highest tumor uptake (3.63 ± 0.32%ID/g at 0.5 h) and excellent tumor/nontumor contrast (7.65 ± 1.14 at 1 h). The tracer remained stable in blood for over 2 h without causing toxicity. These findings highlight CTSD as a key Cancer biomarker and demonstrate the potential of this radiotracer for improving early Cancer detection and monitoring therapy response in patients.

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