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

Xiaoke Niu^1,2, Sixuan Cheng³, Shengping Zhang¹

¹School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Journal of Medicinal Chemistry

|March 5, 2026

Summary

A new bivalent probe, [68Ga]Ga-IPM-N001, targets carbonic anhydrase IX (CAIX) in tumors. This agent shows high tumor uptake and retention, offering promise for clear cell renal cell carcinoma theranostics.

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Area of Science:

Oncology
Radiochemistry
Molecular Imaging

Background:

Carbonic anhydrase IX (CAIX) is overexpressed in hypoxic tumor cells, making it a target for cancer diagnosis and therapy.
Enhancing tumor uptake and pharmacokinetics of CAIX-targeting agents is crucial for effective theranostics.

Purpose of the Study:

To design and evaluate novel bivalent CAIX-targeting probes with integrated hypoxia-sensitive moieties.
To assess the potential of [68Ga]Ga-IPM-N001 as a theranostic agent for clear cell renal cell carcinoma.

Main Methods:

Synthesis of bivalent CAIX-targeting probes incorporating a 2-nitroimidazole moiety into the DPI-4452 scaffold.
PET/CT imaging studies in OS-RC-2 tumor-bearing mice to evaluate tumor uptake and biodistribution.
Surface plasmon resonance (SPR) analysis to determine CAIX-binding affinity.

Main Results:

[68Ga]Ga-IPM-N001 demonstrated superior tumor uptake and significantly improved tumor-to-background ratios (T/K and T/L > 5.0).
The probe exhibited rapid clearance from normal organs (gallbladder, intestines, kidneys) with prolonged tumor retention.
The precursor IPM-N001 showed comparable or improved CAIX-binding affinity to DPI-4452.

Conclusions:

The novel nitroimidazole-containing bivalent agent [68Ga]Ga-IPM-N001 shows significant promise for clear cell renal cell carcinoma theranostics.
Its favorable pharmacokinetic profile and high tumor retention suggest reduced systemic toxicity.
This agent represents a potential advancement in targeted cancer imaging and therapy.