Abstract
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Objectives To quantify the CXCR4-expression by 68Ga-SDF-1α PET for serial in-vivo therapy monitoring and for risk stratification in the murine model of myocardial infarction (MI).
Methods On days 1-6 after MI in C57BL/6 mice, 20 MBq 68Ga-SDF-1α were intravenously injected. Hearts were removed 60 min after tracer application and sectioned. Autoradiography was performed for 24h and the target-to-background ratio (TBR) was determined in the infarcted area. In another group of animals dynamic 68Ga-SDF-1α PET scans were performed on days 1-6 after MI (20 MBq, duration 90 min). These were followed by static 18F-FDG scans (20 MBq, duration 30 min) to determine myocardial viability and for anatomical landmarking. The percentage of the injected dose (% ID/g) of the tracer uptake was calculated. Additionally, hearts were fixated, sectioned and stained immunohistochemically.
Results Quantification of cardiac CXCR4 expression is feasible both ex-vivo and in-vivo. In the autoradiography the TBR was 3.6±1.7 (day 1), it increased up to 4.9±1.5 (day 2; P<0.05 vs. day 1) and a subsequently decreased to 2.2±0.5 (day 6, P<0.05 vs. day 2). The 68Ga-SDF-1α PET showed an equal trend (day 1: 5.37±4.22% ID/g, day 3: 9.64±4.94 %ID/g and day 6: 1.59 %ID/g, P=0.39 day 3 vs. 1). 18F-FDG PET revealed a consistently impaired glucose utilization in the infarcted area over the course of the 6 days. Immunohistochemistry showed an increased CXCR4 expression co-located with the maximum tracer uptake in the autoradiography.
Conclusions Non-invasive quantification of myocardial CXCR4 expression after MI is possible. Maximum tracer uptake is reached on days 2-3 after MI. This might therefore provide the optimal imaging window for risk stratification and monitoring of therapies that affect the SDF-1α/CXCR4 chemokine axis.