The synthesis of a new cardiac sympathetic nerve imaging agent N-[11C]CH3-dopamine and biodistribution study
- 150 Downloads
In this study, we synthesized and characterized N-[11C]methyl-dopamine ([11C]MDA) for cardiac sympathetic nerve imaging. [11C]MDA was synthesized by direct N-methylation of dopamine with [11C]methyl iodide and purified by semi-preparation reverse high pressure liquid chromatography (HPLC). The total synthesis time was 45 min including HPLC purification. The radiochemical yields of [11C]MDA was 20 ± 3 %, without decay correction. The radiochemical purity was >98 % and the specific activity was about 50 GBq/mmol. The biological properties of [11C]MDA were evaluated by biodistribution study in normal mice. PET imaging was performed in healthy Chinese mini-swines. Biodistribution study showed that [11C]MDA had high myocardium uptake. PET/CT imaging showed [11C]MDA had clear and symmetrical myocardium uptake, which was blocked obviously by injecting imipramine hydrochloride. [11C]MDA would be a promising candidate of radiotracer for cardiac sympathetic nervous system imaging.
KeywordsN-[11C]CH3-dopamine Myocardial innervation Sympathetic imaging
This study was supported by Grant from National Natural Science foundation of China (81060019) and Natural Science foundation of Inner Mongolia (2012MS1127 and 2012ZD11) and Natural Science foundation of Inner Mongolia Higher Scientific Research Project (NJZY11124).
- 2.Sasano T, Abraham MR, Chang KC, Ashikaga H, Mills KJ, Holt DP, Hilton J, Nekolla SG, Dong J, Lardo AC, Halperin H, Dannals RF, Marban E, Bengel FM (2008) Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction. J Am Coll Cardiol 51(23):2266–2275. doi: 10.1016/j.jacc.2008.02.062 CrossRefGoogle Scholar
- 4.Huikuri HV, Raatikainen MJ, Moerch-Joergensen R, Hartikainen J, Virtanen V, Boland J, Anttonen O, Hoest N, Boersma LV, Platou ES, Messier MD, Bloch-Thomsen PE (2009) Prediction of fatal or near-fatal cardiac arrhythmia events in patients with depressed left ventricular function after an acute myocardial infarction. Eur Heart J 30(6):689–698. doi: 10.1093/eurheartj/ehn537 CrossRefGoogle Scholar
- 9.Goldstein DS, Eisenhofer G, Dunn BB, Armando I, Lenders J, Grossman E, Holmes C, Kirk KL, Bacharach S, Adams R et al (1993) Positron emission tomographic imaging of cardiac sympathetic innervation using 6-[18F]fluorodopamine: initial findings in humans. J Am Coll Cardiol 22(7):1961–1971CrossRefGoogle Scholar
- 10.Eskola O, Gronroos TJ, Naum A, Marjamaki P, Forsback S, Bergman J, Lankimaki S, Kiss J, Savunen T, Knuuti J, Haaparanta M, Solin O (2012) Novel electrophilic synthesis of 6-[18F]fluorodopamine and comprehensive biological evaluation. Eur J Nucl Med Mol Imaging 39(5):800–810. doi: 10.1007/s00259-011-2032-5 CrossRefGoogle Scholar
- 12.Ilias I, Chen CC, Carrasquillo JA, Whatley M, Ling A, Lazurova I, Adams KT, Perera S, Pacak K (2008) Comparison of 6-[18F]fluorodopamine PET with [123I]metaiodobenzylguanidine and [111In]pentetreotide scintigraphy in localization of nonmetastatic and metastatic pheochromocytoma. J Nucl Med 49(10):1613–1619. doi: 10.2967/jnumed.108.052373 CrossRefGoogle Scholar
- 13.Timmers HJ, Chen CC, Carrasquillo JA, Whatley M, Ling A, Havekes B, Eisenhofer G, Martiniova L, Adams KT, Pacak K (2009) Comparison of [18F]fluoro-L-DOPA, [18F]fluoro-deoxyglucose, and [18F]fluorodopamine PET and [123I]-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma. J Clin Endocrinol Metab 94(12):4757–4767. doi: 10.1210/jc.2009-1248 CrossRefGoogle Scholar
- 15.Raffel DM, Corbett JR, del Rosario RB, Gildersleeve DL, Chiao PC, Schwaiger M, Wieland DM (1996) Clinical evaluation of carbon-11-phenylephrine: MAO-sensitive marker of cardiac sympathetic neurons. J Nucl Med 37(12):1923–1931Google Scholar
- 17.Nguyen NT, DeGrado TR, Chakraborty P, Wieland DM, Schwaiger M (1997) Myocardial kinetics of carbon-11-epinephrine in the isolated working rat heart. J Nucl Med 38(5):780–785Google Scholar