PET imaging and pharmacological therapy targeting carbonic anhydrase-IX high-expressing tumors using US2 platform...

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Carbonic anhydrase-IX (CA-IX) is a promising cancer target due to its association with poor patient prognosis.
• Previous research developed ureidosulfonamide (US2) scaffolds for 111In/90Y radiotheranostics targeting CA-IX.
• The US2 platform's potential for PET imaging and radionuclide therapy needs further exploration.

Purpose of the Study:

• To adapt the US2 platform for Positron Emission Tomography (PET) imaging using 68Ga and for radionuclide therapy using natIn.
• To evaluate the efficacy of 68Ga-US2 for PET imaging and natIn-US2 for therapeutic applications in CA-IX-expressing tumors.

Main Methods:

• In vitro cell binding assays were performed using CA-IX high-expressing (HT-29) and low-expressing (MDA-MB-231) cell lines.
• Biodistribution studies were conducted in tumor-bearing mice using 67Ga-US2 (a surrogate for 68Ga-US2).
• PET imaging was performed using 68Ga-US2, and therapeutic effects of natIn-US2 were assessed in tumor-bearing mice.

Main Results:

• 67Ga-US2 demonstrated significant binding to CA-IX high-expressing HT-29 cells and accumulated in HT-29 tumors in vivo.
• PET imaging with 68Ga-US2 successfully visualized HT-29 tumors in mice.
• Administration of natIn-US2 resulted in tumor growth delay and prolonged survival in mice without significant toxicity.

Conclusions:

• The US2 platform, functionalized with 68Ga and natIn, shows potential as a theranostic agent for CA-IX-expressing cancers.
• 68Ga-US2 is suitable for PET imaging, while natIn-US2 demonstrates therapeutic efficacy.
• The US2 scaffold represents a versatile platform for developing novel cancer theranostic agents targeting CA-IX.