MicroPET Imaging of Riboflavin Transporter 3 Expression in Myocardial Infarction/Reperfusion Rat Models with Radiofluorinated Riboflavin

IF 4.9 Q1 CHEMISTRY, MEDICINAL ACS Pharmacology and Translational Science Pub Date : 2024-07-25 DOI:10.1021/acsptsci.4c0017510.1021/acsptsci.4c00175

Jindian Li, Xingfang Hong, Yingxi Chen, Bin Yin, Hongzhang Yang, Changrong Shi, Xinying Zeng, Deliang Zhang*, Zhide Guo* and Xianzhong Zhang*,

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Abstract

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 ¹⁸F-RFTA in a preclinical rat model of MI/R. The tracer ¹⁸F-RFTA was radio-synthesized manually and characterized on the subjects of radiolabeling yield, radiochemical purity, and stability in vivo. 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 (^99mTc-MIBI). Positron emission tomography (PET) imaging of MI/R and sham-operated rat models were conducted with ¹⁸F-RFTA. Ex vivo autoradiography and RFVT3 immunohistochemical (IHC) staining were conducted to verify the RFVT3 expression in infarcted and normal myocardium. ¹⁸F-RFTA injection was prepared with high radiochemical purity (>95%) and kept stable in vitro and in vivo. ¹⁸F-RFTA PET revealed significant uptake in the infarcted myocardium at 8 h after reperfusion, as confirmed by lower ^99mTc-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 ex vivo 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. ¹⁸F-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.

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用放射性荧光核黄素对心肌梗死/再灌注大鼠模型中核黄素转运体 3 的表达进行显微 PET 成像分析

核黄素转运体 3（RFVT3）是心肌梗塞/再灌注（MI/R）后能量代谢重编程的潜在心脏保护生物靶标。本研究在心肌梗死/再灌注临床前大鼠模型中使用放射性标记探针 18F-RFTA 对心肌梗死/再灌注后 RFVT3 表达的无创实时定量进行了可行性研究。示踪剂 18F-RFTA 是人工放射性合成的，其特征在于放射性标记的产量、放射化学纯度和在体内的稳定性。用锝-99m sestamibi（99mTc-MIBI）进行的心脏磁共振成像（cMRI）和单光子发射计算机断层扫描（SPECT）心肌灌注成像（MPI）证实了 MI/R 和假手术大鼠模型。用 18F-RFTA 对 MI/R 和假手术大鼠模型进行了正电子发射断层扫描（PET）成像。通过体内自显影和 RFVT3 免疫组织化学（IHC）染色来验证 RFVT3 在梗死和正常心肌中的表达。18F-RFTA注射液的放射化学纯度高（95%），在体外和体内均保持稳定。18F-RFTA正电子发射计算机断层显像显示，再灌注后8小时，梗死的心肌有明显的摄取，99m锝-MIBI灌注降低和cMRI强度下降证实了这一点。相反，在正常心肌和受阻的梗死心肌中只有最微量的摄取，体内外自动放射成像进一步证实了这一点。梗死心肌和正常心肌的 IHC 染色进一步证实了 RFVT3 的表达。我们首次证明了对梗死心肌中的 RFVT3 进行成像的可行性。18F-RFTA是一种令人鼓舞的正电子发射计算机断层成像探针，可用于成像心肌梗死后线粒体能量代谢重编程过程中具有心脏保护作用的生物靶标RFVT3。心脏保护生物靶标 RFVT3 的无创成像在心肌梗死患者的诊断和治疗中具有潜在价值。

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来源期刊

ACS Pharmacology and Translational Science Medicine-Pharmacology (medical)

CiteScore

10.00

自引率

3.30%

发文量

133

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