2. Academic Validation
  3. Nitroimidazole-Containing [68Ga]Ga-IPM-N001 as a New CAIX-Targeting Radionuclide Tracer

Nitroimidazole-Containing [68Ga]Ga-IPM-N001 as a New CAIX-Targeting Radionuclide Tracer

  • J Med Chem. 2026 Mar 26;69(6):7474-7487. doi: 10.1021/acs.jmedchem.6c00481.
Xiaoke Niu 1 2,  Sixuan Cheng 3,  Shengping Zhang 1,  Hui Zhang 2,  Kang Chen 2,  Guanqiao Zhang 4,  Yaqi Fu 4,  Yichen Xu 2,  Jiang-Jiang Tang 5,  Wenhai Huang 6,  Xiaowu Dong 2,  Peichen Pan 2 7,  Lu Wan 8,  Bo Wang 1,  Ruhong Zhou 4 9 10 11,  Dawei Jiang 3 12,  Peng Teng 2 13 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
  • 2 Institute of Drug Discovery and Design, School of Pharmacy, Zhejiang University, Hangzhou 310058, China.
  • 3 Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei Key Laboratory of Molecular Imaging, Hubei 430022, China.
  • 4 Zhejiang Key Laboratory of Cell and Molecular Intelligent Design and Development, Institute of Quantitative Biology College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
  • 5 Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China.
  • 6 Key Laboratory of Neuropsychiatric Drug Research of Zhejiang Province, Hangzhou Medical College, Hangzhou 310013, China.
  • 7 Zhejiang Key Laboratory of Intelligent Drug Discovery and Development, Jinhua Institute of Zhejiang University, Jinhua 321299, Zhejiang, China.
  • 8 Wuhan Raydif Biotechnology Co., Ltd., Wuhan 430075, China.
  • 9 Shanghai Institute for Advanced Study, Zhejiang University, Shanghai 201203, China.
  • 10 Cancer Center, Zhejiang University, Hangzhou 310058, China.
  • 11 Department of Chemistry, Columbia University, New York, New York 10027, United States.
  • 12 Key Laboratory of Biological Targeted Therapy, the Ministry of Education, Hubei 430022, China.
  • 13 National Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
PMID: 41784166 DOI: 10.1021/acs.jmedchem.6c00481
Abstract

Carbonic Anhydrase IX (CAIX), which is overexpressed in tumor cells under hypoxic stress, is a promising target for Cancer diagnosis and therapy. To enhance tumor uptake and pharmacokinetics, we designed a series of new bivalent CAIX-targeting probes by integrating a hypoxia-sensitive 2-nitroimidazole moiety into the DPI-4452 scaffold. Among these, the new agent [68Ga]Ga-IPM-N001 demonstrated superior higher tumor uptake and significantly improved tumor-to-background ratios (T/K and T/L > 5.0) in the PET/CT imaging studies using OS-RC-2 tumor-bearing mice. This probe also exhibited rapid clearance from the gallbladder, intestines, and kidneys while maintaining strong and prolonged tumor retention, thereby limiting potential systemic toxicity in the normal tissues. Surface plasmon resonance analysis further demonstrated that the precursor IPM-N001 possesses a comparable or improved CAIX-binding affinity relative to DPI-4452. These findings indicate that this nitroimidazole-containing bivalently targeted agent holds promise as a candidate for the theranostics of clear cell renal cell carcinoma.

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