Imaging of carbonic anhydrase IX with an 111In-labeled dual-motif inhibitor

Area of Science:

• Nuclear Medicine
• Oncology
• Radiochemistry

Background:

• Clear cell renal cell carcinoma (ccRCC) is a significant subtype of kidney cancer.
• Carbonic anhydrase IX (CAIX) is a validated biomarker and therapeutic target overexpressed in ccRCC.
• Development of targeted radionuclide-based agents is crucial for effective ccRCC diagnosis and treatment.

Purpose of the Study:

• To develop and evaluate a novel DOTA-conjugated, bivalent ligand (XYIMSR-01) targeting CAIX for ccRCC.
• To assess the in vitro and in vivo performance of the radiolabeled compound [111In]XYIMSR-01.
• To compare the pharmacokinetic properties of [111In]XYIMSR-01 with existing CAIX-targeting probes.

Main Methods:

• Synthesis and radiolabeling of XYIMSR-01 with Indium-111 ([111In]).
• Characterization of specific radioactivity and yield for [111In]XYIMSR-01.
• In vivo evaluation using Single Photon Emission Computed Tomography (SPECT) and biodistribution studies in mice bearing CAIX-expressing ccRCC xenografts.

Main Results:

• [111In]XYIMSR-01 was synthesized with high yield and specific radioactivity.
• Early and significant radiotracer uptake was observed in ccRCC tumors (26% injected dose/gram at 1 h).
• Excellent tumor-to-background ratios were achieved, with exclusive tumor retention by 48 h, surpassing previous CAIX probes.

Conclusions:

• The dual-targeting strategy of XYIMSR-01 effectively targets CAIX for specific ccRCC detection.
• [111In]XYIMSR-01 demonstrates promising diagnostic potential for ccRCC.
• The developed radiotracer exhibits superior pharmacokinetic properties compared to existing CAIX-targeting agents.