Targeting post-infarct myocardial inflammation - Comparison ¹⁸F-FDG, ⁶⁸Gallium, and ⁶⁸Ga-Dotatate in mice

Objectives Inflammation post myocardial infarction (MI) is emerging as a therapeutic target for endogenous healing. ¹⁸F-FDG has been used for myocardial inflammation imaging but requires cardiomyocyte uptake suppression. We evaluated the suitability of alternative PET inflammation markers: ⁶⁸Gallium(Ga) citrate, the PET analogue of ⁶⁷Ga and ⁶⁸Ga-dotatate, which binds to inflammatory cell somatostatin receptors.

Methods MI was induced in C57Bl/6 mice (n=9) by ligation of the left anterior descending coronary artery. Serial PET scans were acquired at 3-7 days with Ga, Dotatate, or with FDG under ketamine/xylazine for suppression of myocyte uptake. ¹³N-NH₃ PET and contrast-enhanced CT were conducted 7 days after MI for perfusion and cardiac geometry. PET images were analyzed as %ID/g. Regions of interest from NH₃ images identified infarct, border zone, remote myocardium, and ventricular blood pool.

Results MI mice exhibited a 20-30% perfusion defect localized to the anterolateral wall. Contrast-enhanced CT showed moderate anterolateral wall thinning. Histopathology confirmed post-infarct inflammation. Accumulation of FDG under ketamine/xylazine was apparent in the infarct region, but also in border zone and remote myocardium. Ga images showed high blood pool and no specific myocardial uptake until 90min after injection . Dotatate images showed rapid blood clearance, but very limited myocardial uptake which was not different from background.

Conclusions Gallium does not exhibit sufficient blood clearance and signal specificity to identify myocardial inflammation in MI mice. Lack of binding of dotatate suggests that somatostatin receptors are not robustly expressed in acute stages post MI. FDG accumulation under ketamine/xylazine remains the most reliable and robust approach for further studies of post-MI inflammation.