In vivo imaging of human monocyte localization in the early and late inflammatory phase of mouse myocardial infarction

Ziel/Aim Distinct infiltration patterns of human monocytes during different phases of infarct healing could have an effect on the remodelling process and might be altered in patients with cardiovascular diseases. Here, we established an in vivo imaging approach to track human monocytes in mice with myocardial infarction (MI) to study their post-ischemic infiltration and behaviour.

Methodik/Methods Human CD14⁺⁺ CD16^- monocytes were labelled with Tc-99m-HMPAO and the fluorescent dye DiD. NOD/Scid mice underwent surgery for permanent ligation of the LAD or a control sham surgery. Area at risk (AAR) was determined by Tc-99m-tetrofosmin SPECT/CT following surgery. On day 1 or 3 post-MI, 10 × 10⁶ dual-labelled human monocytes were injected i.v. In vivo SPECT/CT scans were acquired 18h p.i. (i.e. 2 or 4 days post-MI). Subsequently, organs were explanted and assessed for biodistribution by ex vivo SPECT/CT, fluorescence reflectance imaging (FRI), autoradiography (AR), and gamma counter analysis.

Ergebnisse/Results Cells were detected in vivo in the AAR by SPECT imaging on day 2 and 4 post-MI. In and ex vivo SPECT scans of the heart revealed that cells mainly accumulated in the border zone on day 2 post-MI. In contrast, on day 4 post-MI, they accumulated more homogeneously within the infarct area. Similar results were obtained with ex vivo FRI of tissue sections. Quantification displayed higher signals in the AAR of MI mice when compared to remote myocardium and sham mice on day 2 and 4 post-MI. Linear regression analysis revealed that monocyte infiltration increases with infarct size.

Schlussfolgerungen/Conclusions By using a non-invasive in vivo imaging approach, we have shown that human monocytes accumulate in distinct regions of the infarcted myocardium in different phases of healing following murine MI. These results are in accordance with observations made in ischemic human hearts post-mortem, indicating that the presented imaging model can be a valuable tool to further characterize human immune cells in vivo in the context of MI.