In vivo monitoring of PTH therapy after myocardial infarction in mice using [68Ga]-Annexin-V/[18F]-FDG micro PET

Abstract

Aim: We intended to analyze the antiapoptotic effect of parathyroid hormone (PTH) after induced myocardial infarction in mice using a [68Ga]-Annexin-V/[18F]-FDG microPET imaging protocol. Methods: We induced a myocardial infarction in female wildtype mice (C57/Bl6) via permanent ligation of the LAD. Mice were treated either with PTH or with saline as control. At day 2 after myocardial infarction, we injected 15 MBq [68Ga]-Annexin-V, and PET acquisition lasting 90 minutes was initiated. At day 6 and day 30 after myocardial infarction, we injected 20 MBq [18F]-FDG, and a list mode PET acquisition lasting 30 minutes was acquired. Standard volumes of interest (VOI) were drawn around the region of most intense [68Ga]Annexin V accumulation. The mean radioactivity concentration within the VOI was quantified as the percentage of the injected dose per gram (%ID/g), and correlated to histological findings after TUNEL staining. Further, we analyzed the size of infarction, the endsystolic volume (ESV), and the left ventricular ejection fraction (LVEF) by [18F]-FDG-PET. Results: Annexin uptake at day 2 after myocardial infarction was significantly reduced in PTH treated mice (PTH: 4.5±1.9%ID/g vs. control 7.1±1.1%ID/g, P<0.05). There was a very good correlation of Annexin uptake with the number of TUNEL positiv cells (PTH: 54±16% vs. Control 63±25%). The size of infarction was significantly reduced from day 6 to day 30 in PTH treated mice. Further, ESV was significantly reduced and LVEF improved after PTH treatment. Conclusion: We could demonstrate, that in vivo monitoring of the cardioprotective effects of PTH after myocardial infarction in mice using microPET is feasible. We could show the antiapoptotic effect as well as the effects on size of infarction and cardiac function.