SPECT Imaging of Cardiac Inflammation by Targeting IL4 Receptor-α on Macrophages

The inflammation response is a prominent sign of myocardial infarction (MI), mediating the process of cardiac fibrosis and ventricular remodeling. Inflammation visualization holds new promise for guiding cardiac anti-inflammatory therapy. Interleukin-4 receptor α (IL4Rα) interacts with IL4, closely related to macrophage polarization. This study aimed to evaluate the feasibility of a technetium-99m (^99mTc) labeled IL4Rα antibody probe ([^99mTc]Tc-HYNIC-CM310) for targeting postinfarction macrophage SPECT imaging. [^99mTc]Tc-HYNIC-CM310 was prepared by radiolabeling an IL4Rα-specific monoclonal antibody (CM310) with ^99mTc. Images were acquired at 0.5, 6, 12, 24, and 36 h postinjection on the next day after MI and the sham model preparation, and a biodistribution study was performed at 36 h. The mean percentage of injected dose per gram (%ID/g) of various tissues was obtained by drawing the regions of interest. [¹⁸F]FDG myocardial metabolism and inflammation imaging were performed for comparison and verification. Immunofluorescence costaining and flow cytometry were conducted to validate the coexpression of IL4Rα and macrophages. The radiolabeling yield of [^99mTc]Tc-HYNIC-CM310 was approximately 88.31% ± 1.70%, and the radiochemical purity was 93.70% ± 0.38%. The accumulation of [^99mTc]Tc-HYNIC-CM310 in infarcted myocardium was increased starting at 12 h postinjection. The tracer uptake was significantly higher in the infarcted myocardium than the same site in sham-operated rats (P < 0.05). The tracer uptake region was consistent with the cardiac metabolic defect and inflammatory region seen by [¹⁸F]FDG PET. Immunofluorescence staining and flow cytometry confirmed the colocalization of IL4Rα⁺ cells and macrophage markers in the infarcted myocardium. We successfully prepared and validated the SPECT probe [^99mTc]Tc-HYNIC-CM310 for precise visualization of macrophages, offering a new opportunity for guiding the treatment of cardiac inflammation.