Noninvasive Imaging of Immune Cell Activity in Myocardial Infarction Phases Using ^99mTc-HYNIC-mAb_Kv1.3 SPECT/CT

Acute myocardial infarction (MI) remains a leading cause of mortality worldwide, with inflammatory and reparative phases playing critical roles in disease progression. Currently, there is a pressing need for in vivo imaging techniques to monitor immune cell infiltration and inflammation activity during these phases. We developed a novel probe, ^99mTc-HYNIC-mAb_Kv1.3, utilizing a monoclonal antibody that targets the voltage-gated potassium channel 1.3 (Kv1.3). This probe enables in vivo visualization of immune cells that express high levels of Kv1.3 proteins. In a murine MI model, SPECT/CT imaging with ^99mTc-HYNIC-mAb_Kv1.3 demonstrated specific uptake in an infarcted myocardium during the inflammatory phase, reflecting immune cell infiltration and activity. During the reparative phase, the probe exhibited prolonged retention in the infarcted area, suggestive of ongoing immune cell proliferation. Immunofluorescence staining confirmed the probe's specificity. Biodistribution analysis indicated preferential accumulation in the infarcted myocardium and liver, consistent with SPECT/CT findings. Combined with [¹⁸F]FDG PET/CT, these modalities provided comprehensive insights into myocardial viability and inflammation. This study highlights the potential of ^99mTc-HYNIC-mAb_Kv1.3 SPECT/CT as a noninvasive tool to monitor immune cell activity in different phases of MI, guide therapeutic interventions, and predict disease progression. Further translational studies are warranted to explore its clinical applicability in cardiac pathologies.