Li Jindian, Hong Xingfang, Chen Yingxi, Yin Bin, Yang Hongzhang, Shi Changrong, Zeng Xinying, Zhang Deliang, Guo Zhide, Zhang Xianzhong
Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Center for Molecular Imaging and Translational Medicine, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China.
ACS Pharmacol Transl Sci. 2024 Jul 26;7(8):2350-2357. doi: 10.1021/acsptsci.4c00175. eCollection 2024 Aug 9.
Riboflavin transporter 3 (RFVT3) represents a potential cardioprotective biotarget in energetic metabolism reprogramming after myocardial infarction/reperfusion (MI/R). This study investigated the feasibility of noninvasive real-time quantification of RFVT3 expression after MI/R with an radiolabeled probe F-RFTA in a preclinical rat model of MI/R. The tracer F-RFTA was radio-synthesized manually and characterized on the subjects of radiolabeling yield, radiochemical purity, and stability . MI/R and sham-operated rat models were confirmed by cardiac magnetic resonance imaging (cMRI) and single-photon-emission computed tomography (SPECT) myocardial perfusion imaging (MPI) with technetium-99m sestamibi (Tc-MIBI). Positron emission tomography (PET) imaging of MI/R and sham-operated rat models were conducted with F-RFTA. autoradiography and RFVT3 immunohistochemical (IHC) staining were conducted to verify the RFVT3 expression in infarcted and normal myocardium. F-RFTA injection was prepared with high radiochemical purity (>95%) and kept stable and . F-RFTA PET revealed significant uptake in the infarcted myocardium at 8 h after reperfusion, as confirmed by lower Tc-MIBI perfusion and decreased intensity of cMRI. Conversely, there were only the tiniest uptakes in the normal myocardium and blocked infarcted myocardium, which was further corroborated by autoradiography. The RFVT3 expression was further confirmed by IHC staining in the infarcted and normal myocardium. We first demonstrate the feasibility of imaging RFVT3 in infarcted myocardium. F-RFTA is an encouraging PET probe for imaging cardioprotective biotarget RFVT3 in mitochondrial energetic metabolism reprogramming after myocardial infarction. Noninvasive imaging of cardioprotective biotarget RFVT3 has potential value in the diagnosis and therapy of patients with MI.
核黄素转运体3(RFVT3)是心肌梗死/再灌注(MI/R)后能量代谢重编程中一种潜在的心脏保护生物靶点。本研究在MI/R的临床前大鼠模型中,研究了使用放射性标记探针F-RFTA对MI/R后RFVT3表达进行无创实时定量的可行性。示踪剂F-RFTA通过手工进行放射性合成,并对放射性标记产率、放射化学纯度和稳定性进行了表征。MI/R和假手术大鼠模型通过心脏磁共振成像(cMRI)和使用锝-99m甲氧基异丁基异腈(Tc-MIBI)的单光子发射计算机断层扫描(SPECT)心肌灌注成像(MPI)进行确认。使用F-RFTA对MI/R和假手术大鼠模型进行正电子发射断层扫描(PET)成像。进行放射自显影和RFVT3免疫组织化学(IHC)染色,以验证梗死心肌和正常心肌中RFVT3的表达。F-RFTA注射剂具有高放射化学纯度(>95%)且保持稳定。F-RFTA PET显示再灌注后8小时梗死心肌中有明显摄取,这通过较低的Tc-MIBI灌注和cMRI强度降低得到证实。相反,正常心肌和梗死心肌梗死区仅有微量摄取,放射自显影进一步证实了这一点。RFVT3的表达通过梗死心肌和正常心肌的IHC染色进一步得到证实。我们首次证明了在梗死心肌中对RFVT3进行成像的可行性。F-RFTA是一种令人鼓舞的PET探针,可用于在心肌梗死后线粒体能量代谢重编程中对心脏保护生物靶点RFVT3进行成像。心脏保护生物靶点RFVT3的无创成像在MI患者的诊断和治疗中具有潜在价值。