PMID- 29936643 OWN - NLM STAT- MEDLINE DCOM- 20190917 LR - 20190917 IS - 1573-675X (Electronic) IS - 1360-8185 (Linking) VI - 23 IP - 7-8 DP - 2018 Aug TI - PET imaging of cardiomyocyte apoptosis in a rat myocardial infarction model. PG - 396-407 LID - 10.1007/s10495-018-1463-x [doi] AB - Cardiomyocyte apoptosis has been observed in several cardiovascular diseases and contributes to the subsequent cardiac remodeling processes and progression to heart failure. Consequently, apoptosis imaging is helpful for noninvasively detecting the disease progression and providing treatment guidance. Here, we tested (18)F-labeled 2-(5-fluoropentyl)-2-methyl-malonic acid ((18)F-ML-10) and (18)F-labeled 2-(3-fluoropropyl)-2-methyl-malonic acid ((18)F-ML-8) for apoptosis imaging in rat models of myocardial infarction (MI) and compared them with (18)F-fluorodeoxyglucose ((18)F-FDG). MI was induced in Sprague-Dawley rats by permanent left coronary artery ligation. Procedural success was confirmed by echocardiography and positron emission tomography (PET) imaging with (18)F-FDG. In vivo PET imaging with (18)F-ML-10 and (18)F-ML-8 was performed in the MI models at different time points after operation. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assays and immunohistochemical analyses were used to evaluate myocardial apoptosis. In vitro cell binding assays were performed to validate (18)F-ML-8 binding to apoptotic cardiomyocytes. PET imaging demonstrated high (18)F-ML-10 and (18)F-ML-8 uptake where (18)F-FDG uptake was absent. The focal accumulation of the two tracers was high on days 1 and 3 but was not notable on days 5 and 7 after surgery. The infarct-to-lung uptake ratio was 4.29 +/- 0.30 for (18)F-ML-10 and 3.51 +/- 0.18 for (18)F-ML-8 (n = 6, analyzed by averaging the uptake ratios on postoperative days 1 and 3, P < 0.05). The TUNEL results showed that myocardial cell apoptosis was closely related to the focal uptake of the apoptotic tracers in the infarct area. In addition, the apoptosis rates calculated from the TUNEL results were better correlated with (18)F-ML-8 uptake than with (18)F-ML-10 uptake. Ex vivo cell binding assays demonstrated that (18)F-ML-8 accumulated in apoptotic cells but not in necrotic or normal cells. PET imaging using (18)F-ML-10 or (18)F-ML-8 allows the noninvasive detection of myocardial apoptosis in the early phase. In addition, (18)F-ML-8 may be better than (18)F-ML-10 for apoptosis imaging. We propose that PET imaging with (18)F-ML-10 or (18)F-ML-8 combined with (18)F-FDG is an alternative for detecting and assessing MI. FAU - Ma, Hui AU - Ma H AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Liu, Shaoyu AU - Liu S AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Xiong, Ying AU - Xiong Y AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Zhang, Zhanwen AU - Zhang Z AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Sun, Aixia AU - Sun A AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Su, Shu AU - Su S AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Liang, Hong AU - Liang H AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. liangh1688@126.com. FAU - Yuan, Gongjun AU - Yuan G AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. FAU - Tang, Ganghua AU - Tang G AUID- ORCID: 0000-0003-2639-0388 AD - Department of Nuclear Medicine and Guangdong Engineering Research Center for the Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. gtang0224@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Apoptosis JT - Apoptosis : an international journal on programmed cell death JID - 9712129 RN - 0 (Fluorine Radioisotopes) RN - 0Z5B2CJX4D (Fluorodeoxyglucose F18) SB - IM MH - Animals MH - Apoptosis/physiology MH - Disease Models, Animal MH - Fluorine Radioisotopes/metabolism MH - Fluorodeoxyglucose F18 MH - Myocardial Infarction/*metabolism MH - Myocardium/*metabolism MH - Myocytes, Cardiac/*metabolism MH - *Positron-Emission Tomography/methods MH - Rats, Sprague-Dawley OTO - NOTNLM OT - 18F-ML-10 OT - 18F-ML-8 OT - Apoptosis OT - Myocardial infarction OT - PET EDAT- 2018/06/25 06:00 MHDA- 2019/09/19 06:00 CRDT- 2018/06/25 06:00 PHST- 2018/06/25 06:00 [pubmed] PHST- 2019/09/19 06:00 [medline] PHST- 2018/06/25 06:00 [entrez] AID - 10.1007/s10495-018-1463-x [pii] AID - 10.1007/s10495-018-1463-x [doi] PST - ppublish SO - Apoptosis. 2018 Aug;23(7-8):396-407. doi: 10.1007/s10495-018-1463-x.