PMID- 30042495 OWN - NLM STAT- MEDLINE DCOM- 20191023 LR - 20191023 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 8 IP - 1 DP - 2018 Jul 24 TI - The Impact of Ageing on 11C-Hydroxyephedrine Uptake in the Rat Heart. PG - 11120 LID - 10.1038/s41598-018-29509-0 [doi] LID - 11120 AB - We aimed to explore the impact of ageing on 11C-hydroxyephedrine (11C-HED) uptake in the healthy rat heart in a longitudinal setting. To investigate a potential cold mass effect, the influence of specific activity on cardiac 11C-HED uptake was evaluated: 11C-HED was synthesized by N-methylation of (-)-metaraminol as the free base (radiochemical purity >95%) and a wide range of specific activities (0.2-141.9 GBq/mumol) were prepared. (11)C-HED (48.7 +/- 9.7MBq, ranged 0.2-60.4 mug/kg cold mass) was injected in healthy Wistar Rats. Dynamic 23-frame PET images were obtained over 30 min. Time activity curves were generated for the blood input function and myocardial tissue. Cardiac 11C-HED retention index (%/min) was calculated as myocardial tissue activity at 20-30 min divided by the integral of the blood activity curves. Additionally, the impact of ageing on myocardial 11C-HED uptake was investigated longitudinally by PET studies at different ages of healthy Wistar Rats. A dose-dependent reduction of cardiac 11C-HED uptake was observed: The estimated retention index as a marker of norepinephrine function decreased at a lower specific activity (higher amount of cold mass). This observed high affinity of 11C-HED to the neural norepinephrine transporter triggered a subsequent study: In a longitudinal setting, the 11C-HED retention index decreased with increasing age. An age-related decline of cardiac sympathetic innervation could be demonstrated. The herein observed cold mass effect might increase in succeeding scans and therefore, 11C-HED microPET studies should be planned with extreme caution if one single radiosynthesis is scheduled for multiple animals. FAU - Werner, Rudolf A AU - Werner RA AD - Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany. AD - The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD, United States. AD - Comprehensive Heart Failure Center (CHFC), University of Wurzburg, Wurzburg, Germany. FAU - Chen, Xinyu AU - Chen X AD - Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany. AD - Comprehensive Heart Failure Center (CHFC), University of Wurzburg, Wurzburg, Germany. FAU - Maya, Yoshifumi AU - Maya Y AD - Research Centre, Nihon Medi-Physics Co., Ltd., Chiba, Japan. FAU - Eissler, Christoph AU - Eissler C AD - Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany. FAU - Hirano, Mitsuru AU - Hirano M AD - Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany. AD - Comprehensive Heart Failure Center (CHFC), University of Wurzburg, Wurzburg, Germany. FAU - Nose, Naoko AU - Nose N AD - Department of Biomedical Imaging, National Cerebral and Cardiovascular Center, Suita, Japan. FAU - Wakabayashi, Hiroshi AU - Wakabayashi H AD - Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany. AD - Comprehensive Heart Failure Center (CHFC), University of Wurzburg, Wurzburg, Germany. FAU - Lapa, Constantin AU - Lapa C AD - Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany. FAU - Javadi, Mehrbod S AU - Javadi MS AD - The Russell H. Morgan Department of Radiology and Radiological Science, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine, Baltimore, MD, United States. FAU - Higuchi, Takahiro AU - Higuchi T AD - Department of Nuclear Medicine, University of Wurzburg, Wurzburg, Germany. thiguchi@me.com. AD - Comprehensive Heart Failure Center (CHFC), University of Wurzburg, Wurzburg, Germany. thiguchi@me.com. AD - Department of Biomedical Imaging, National Cerebral and Cardiovascular Center, Suita, Japan. thiguchi@me.com. LA - eng GR - 1789/3-3/Deutsche Forschungsgemeinschaft (German Research Foundation)/International PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180724 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Carbon Radioisotopes) RN - 3002-40-2 (3-hydroxyephedrine) RN - 818U2PZ2EH (Metaraminol) RN - GN83C131XS (Ephedrine) SB - IM MH - Aging/*metabolism/pathology MH - Animals MH - Carbon Radioisotopes/administration & dosage MH - Ephedrine/administration & dosage/*analogs & derivatives MH - Heart/*diagnostic imaging/innervation/physiology MH - Humans MH - Metaraminol/chemistry MH - Myocardium/*metabolism MH - Positron-Emission Tomography MH - Radionuclide Imaging/methods MH - Rats MH - Rats, Wistar MH - Sympathetic Nervous System MH - Tissue Distribution PMC - PMC6057985 COIS- The authors declare no competing interests. EDAT- 2018/07/26 06:00 MHDA- 2019/10/24 06:00 PMCR- 2018/07/24 CRDT- 2018/07/26 06:00 PHST- 2018/05/16 00:00 [received] PHST- 2018/07/11 00:00 [accepted] PHST- 2018/07/26 06:00 [entrez] PHST- 2018/07/26 06:00 [pubmed] PHST- 2019/10/24 06:00 [medline] PHST- 2018/07/24 00:00 [pmc-release] AID - 10.1038/s41598-018-29509-0 [pii] AID - 29509 [pii] AID - 10.1038/s41598-018-29509-0 [doi] PST - epublish SO - Sci Rep. 2018 Jul 24;8(1):11120. doi: 10.1038/s41598-018-29509-0.