Novel PET/CT tracers for targeted imaging of membrane receptors to evaluate cardiomyocyte apoptosis and tissue repair process in a rat model of myocardial infarction

作者:Sun, Ting*; Wei, Lijiang; Tian, Hua*; Zhan, Wanlin; Ma, Hui; Nie, Dahong; Wang, Shilin; Chen, Xin; Tang, Ganghua*
来源:Apoptosis : an international journal on programmed cell death , 2021, 26(7-8): 460-473.
DOI:10.1007/s10495-021-01681-1

摘要

The purpose of this study was to employ novel tracers PET imaging approach to define the time course and intensity of myocardial repair after apoptosis and to correlate the imaging signal to immunohistochemical staining in myocardial infarction (MI). We designed novel alpha(V)beta(3)-targeted and radio-functionalized tracers for detection of apoptosis in H9C2 cells and myocardial tissue. MI rats were imaged with [F-18]FDG, [F-18]ANP-Cin or [F-18]ANP-RGD(2) using a small-animal PET/CT device. Rats were sacrificed, and tissue samples from viable and injured myocardial areas were sectioned for TUNEL assay and histology. The uncorrected radiochemical yield of [F-18]ANP-Cin and [F-18]ANP-RGD(2) were 41.3 +/- 5.4% and 21.17 +/- 4.7%, respectively. Two tracers meet many criteria for cardiac imaging, including high stability, high binding, no toxicity, fast renal clearance and excellent biodistribution in rat models. The uptake of [F-18]ANP-Cin was significantly higher on the 1st and 3rd day than the 7th or 28th day after MI induction, a timeframe associated with increased cardiomyocyte apoptosis. Higher uptake of [F-18]ANP-Cin was observed in MI rats than in N-acetylcysteine (NAC)-treated rats on the 3rd days. In contrast with [F-18]ANP-Cin, no hot-spots was observed with [F-18]ANP-RGD(2) on the 1st day and more hot-spots was observed from the 3rd day to the 7th day, then less on the 28th days in the high apoptotic site. There was no uptake of [F-18]FDG in or around the apoptotic region. On the 7th day the uptake of [F-18]ANP-RGD(2) was higher in NAC-treated rats than MI rats. [F-18]ANP-Cin and [F-18]ANP-RGD(2) are superior to [F-18]FDG for PET/CT imaging for evaluation of cardiomyocyte apoptosis and tissue repair processes in the MI rats.

  • 单位
    上海交通大学; 中山大学; 1; 南方医科大学