Browse > Article

A Convenient Radiolabeling of [$^{11}$C](R)-PK11195 Using Loop Method in Automatic Synthesis Module  

Lee, Hak-Jeong (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Jeong, Jae-Min (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Lee, Yun-Sang (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Kim, Hyung-Woo (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Choi, Jae-Yeon (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Lee, Dong-Soo (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Chung, June-Key (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Lee, Myung-Chul (Department of Nuclear Medicine and Institute of Radiation Medicine, Seoul National University College of Medicine)
Publication Information
Nuclear Medicine and Molecular Imaging / v.43, no.4, 2009 , pp. 337-343 More about this Journal
Abstract
Purpose: ((R)-1-(2-chlorophenyl)-N-1-[$^{11}$C]methyl-N(1-propyl)-3-isoquinoline carboxamide ((R)-PK11195) is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a direct and simple radiosynthesis of [$^{11}$C](R)-PK11195 in mild condition using NaH suspension in DMF and one-step loop method. Materials and Methods: (R)-N-Desmethyl-PK11195 (1 mg) in DMSO (0.1 mL) and NaH suspension in DMF (0.1 mL) were injected into a semi-prep HPLC loop. [$^{11}$C]methyl iodide was passed through HPLC loop at room temperature. Purification was performed using semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. Results: The labeling efficiency of [$^{11}$C](R)-PK11195 was 71.8$\pm$8.5%. The specific activity was 11.8:$\pm$6.4 GBq/$\mu$mol and radiochemical purity was higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. Conclusion: By the one-step loop method with the [$^{11}$C]CH3l automated synthesis module, [$^{11}C$](R)-PK11195 could be easily prepared in high radiochemical yield using NaH suspension in DMF.
Keywords
PK11195; microglia; PBR; PET; [$^{11}$C]methyl iodide; loop method;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Chao CC, Hu S, Peterson PK. Modulation of human microglial cell superoxide production by cytokines. J Leukoc Biol 1995;58:65-70   DOI   PUBMED   ScienceOn
2 Parola AL, Yamamura HI, Laird HE. Peripheral-type benzodiazepine receptors. Life Sci 1993;52:1329-42   DOI   ScienceOn
3 Cagnin A, Brooks DJ, Kennedy AM, Gunn RN, Myers R, Turkheimer FE, et al. In-vivo measurement of activated microglia in dementia. Lancet 2001;358:461-7   DOI   ScienceOn
4 Chen MK, Guilarte TR. Imaging the peripheral benzodiazepine receptor response in central nervous system demyelination and remyelination. Toxicol Sci 2006;91:532-9   DOI   ScienceOn
5 Carnsonne R, Crouzel C, Comar D, Maziere M, Prenant C, Sastre J, et al. Synthesis of N-($^{11}$C) methyl, N-(methyl-1 propyl), (chloro-2 phenyl)-1 isoquinoleine carboxamide-3 (PK 11195): A new ligand for peripheral benzodiazepine receptors. J Label Compd Radiopharm 1984;21:985-91   DOI   ScienceOn
6 Hashimoto K, Inoue O, Suzuki K, Yamasaki T, Kojima M. Synthesis and evaluation of $^{11}$C-PK 11195 for in vivo study of peripheral-type benzodiazepine receptors using positron emission tomography. Ann Nucl Med 1989;3:63-71   DOI   ScienceOn
7 Choe YS. Radiolabeling methods used for preparation of molecular probes. Nucl Med Mol Imaging 2004;38:121-30   과학기술학회마을   ScienceOn
8 Wilson AA, Garcia A, Jin L, Houle S. Radiotracer synthesis from [$^{11}$C]-iodomethane: a remarkably simple captive solvent method. Nucl Med Biol 2000;27:529-32   DOI   ScienceOn
9 Rahman O, Kihlberg T, Langstrom B. Synthesis of N-methyl-N-(1-methylpropyl)-1-(2-chlorophenyl)isoquinoline-3-[$^{11}$C]carboxam ide ([$^{11}$C-carbonyl]PK11195) and some analognes using [$^{11}$C]carbon monoxide and 1-(2-chlorophenyl)isoquinolin-3-yl trifiate. J Am Chem Soc Perkin Trans 1 2002:2699-703
10 Schwartz M. Macrophages and microglia in central nervous system injury: are they helpful or harmful? J Cereb Blood Flow Metab 2003;23:385-94   DOI
11 Lee HJ, Jeong JM, Lee Y, Kim HW, Lee E, Lee DS, et al. Radiosynthesis of [$^{11}$C]6-OH-BTA-1 in different media and confirmation of reaction by-products. Nucl Med Mol Imaging 2007;41:241-6   ScienceOn
12 Debruyne JC, Versijpt J, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, et al. PET visualization of microglia in multiple sclerosis patients using [$^{11}$C]PK11195. Eur J Neurol 2003;10:257-64   DOI   ScienceOn
13 Kremlev SG, Roberts RL, Palmer C. Differential expression of chemokines and chemokine receptors during microglial activation and inhibition. J Neroimmunol 2004;149:1-9   DOI   ScienceOn
14 Gerhard A, Watts J, Trender-Gerhard I, Turkheimer F, Banati RB, Bhatia K, et al. In vivo imaging of microglial activation with [$^{11}$C](R)-PK11195 PET in corticobasal degeneration. Mov Disord 2004;19:1221-6   DOI   ScienceOn
15 Gerhard A, Neumaier B, Elitok E, Glatting G, Ries V, Tomczak R, et al. In vivo imaging of activated microglia using [$^{11}$C]PK11195 and positron emission tomography in patients after ischemic stroke. Neuroreport 2000;11:2957-60   DOI   ScienceOn
16 Cremer JE, Hume SP, Cullen BM, Myers R, Manjil LG, Turton DR, et al. The distribution of radioactivity in brains of rats given [N-methyl-$^{11}$C]PK 11195 in vivo after induction of a cortical ischaemic lesion. Int J Rad Appl Instrum B 1992;19:159-66   DOI   PUBMED
17 Rao VL, Bowen KK, Rao AM, Dempsey RJ. Up-regulation of the peripheral-type benzodiazepine receptor expression and [$^{3}$H$]PK11195 binding in gerbil hippocampus after transient forebrain ischemia. J Neurosci Res 2001;64:493-500   DOI   ScienceOn
18 McGeer EG, McGeer PL. The importance of inflammatory mechanisms in Alzheimer disease. Exp Gerontol 1998;33:371-8   DOI   ScienceOn
19 Gerhard A, Schwarz J, Myers R, Wise R, Banati RB. Evolution of microglial activation in patients after ischemic stroke: a [$^{11}C$](R)-PK11195 PET study. Neuroimage 2005;24:591-5   DOI   ScienceOn
20 Larsen P, Ulin J, Dahlstrom K, Jensen M. Synthesis of [$^{11}$C]iodomethane by iodination of [$^{11}$C]methane. Appl Radiat Isot 1997;48:153-7   DOI   ScienceOn
21 Shah F, Hume SP, Pike VW, Ashworth S, McDermott J. Synthesis of the enantiomers of [N-methyl-$^{11}$C]PK11195 and comparison of their behaviours as radioligands for PK binding sites in rats. Nucl Med Biol 1994;21:573-81   DOI   ScienceOn
22 McGeer PL, McGeer EG. Inflammation and neurodegeneration in Parkinson's disease. Parkinsonism Relat Disord 2004;10(Suppl 1):S3-S7   DOI   ScienceOn
23 Pappata S, Levasseur M, Gunn RN, Myers R, Crouzel C, Syrota A, et al. Thalamic microglial activation in ischemic stroke detected in vivo by PET and [$^{11}$C]PK11195. Neurology 2000;55:1052-4   DOI   ScienceOn
24 Turner MR, Cagnin A, Turkheimer FE, Miller CC, Shaw CE, Brooks DJ, et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [$^{11}$C](R)-PK11195 positron emission tomography study. Neurobiol Dis 2004;15:601-9   DOI   ScienceOn
25 Banati RB, Graeber MB. Surveillance, intervention and cytotoxicity: is there a protective role of microglia? Dev Neurosci 1994;16:114-27   DOI   ScienceOn
26 Groom GN, Junck L, Foster NL, Frey KA, Kuhl DE. PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease. J Nucl Med 1995;36:2207-10   PUBMED
27 Cagnin A, Gerhard A, Banati RB. The concept of in vivo imaging of neuroinflammation with [[$^{11}$C](R}-PK11195 PET. Ernst Schering Res Found Workshop 2002:179-91
28 Vowinckel E, Reutens D, Becher B, Verge G, Evans A, Owens T, et al. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res 1997;50:345-53   DOI   ScienceOn
29 Bachman DL, Wolf PA, Linn R, Knoefel JE, Cobb J, Belanger A, et al. Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 1992;42:115-9   DOI   PUBMED
30 Henkel K, Karitzky J, Schmid M, Mader I, Glatting G, Unger JW, et al. Imaging of activated microglia with PET and [$^{11}$C]PK11195 in corticobasal degeneration. Mov Disord 2004;19:817-21   DOI   ScienceOn
31 Debruyne JC, Van Laere KJ, Versijpt J, De Vos F, Keppen J, Strijckmans K, et al. Semiquantification of the peripheral-type benzodiazepine ligand [[$^{11}$C]PK11195 in normal human brain and application in multiple sclerosis patients. Acta Neurol Belg 2002;102:127-35   PUBMED   ScienceOn
32 Mankowski JL, Queen SE, Tarwater PJ, Adams RJ, Guilarte TR. Elevated peripheral benzodiazepine receptor expression in simian immunodeficiency virus encephalitis. J Neurovirol 2003;9:94-100   DOI   PUBMED   ScienceOn
33 Wilson AA, Garcia A, Chestakova A, Kung H, Houle S. A rapid one-step radiosynthesis of the ${\beta}$-amyloid imaging radiotracer N-methyl-[$^{11}$C]2-(4'-methylaminophenyl)-6-ydroxybenzothiazole ([$^{11}$C]-6-OH-BTA-1). J Label Compd Radiopharm 2004;47:679-82   DOI   ScienceOn
34 Gerhard A, Banati RB, Goerres GB, Cagnin A, Myers R, Gunn RN, et al. [$^{11}$C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology 2003;61:686-9   DOI   PUBMED   ScienceOn
35 Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F, Barker RA, et al. Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 2006;66:1638-43   DOI   ScienceOn
36 Vowinckel E, Reutens D, Becher B, Verge G, Evans A, Owens T, et al. PKI1195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res 1997;50:345-53   DOI   ScienceOn
37 Wang X, Chen S, Ma G, Ye M, Lu G. Involvement of proinflammatory factors, apoptosis, caspase-3 activation and Ca2+ disturbance in microglia activation-mediated dopaminergic cell degeneration. Mech Ageing Dev 2005;126:1241-54   DOI   ScienceOn
38 Koh S. Microglial Imaging in neurological disorders with PK11195 PET. J Korean Soc Clin Neurophysiol 2007;9:91-7
39 Gerhard A, Trender-Gerhard I, Turkheimer F, Quinn NP, Bhatia KP, Brooks DJ. In vivo imaging of microglial activation with [$^{11}$C](R)-PK11195 PET in progressive supranuclear palsy. Mov Disord 2006;21:89-93   DOI   ScienceOn
40 Versijpt J, Debruyne JC, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, et al. Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult Scler 2005;11:127-34   DOI   ScienceOn
41 Crouzel C, Langstrom B, Pike VW, Coenen HH. Recommendations for a practical production of [$^{11}$C]methyl iodide. Appl Radiat Isot 1987;38:601-3   DOI   ScienceOn
42 Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, et al. In vivo imaging of microglial activation with [$^{11}$C](R)PK11195 PET in idiopathic Parkinson's disease. Neurobiol Dis 2006;21:404-12   DOI   ScienceOn
43 Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, et al. Early and progressive acclUl1ulation of reactive microglia in the Huntington disease brain. J Neuropathol Exp Neurol 2001;60:161-72   DOI   ScienceOn
44 Hammoud DA, Endres CJ, Chander AR, Guilarte TR, Wong DF, Sacktor NC, et al. Imaging glial cell activation with [$^{11}$C]-RPK11195 in patients with AIDS. J Neurovirol 2005;11:346-55   DOI   ScienceOn
45 Banati RE, Newcombe J, Gunn RN, Cagnin A, Turkheimer F, Heppner F, et al. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 2000;123:2321-37   DOI   ScienceOn
46 Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, et al. Microglial activation in presymptomatic Huntington's disease gene carriers. Brain 2007;130:1759-66   DOI   ScienceOn
47 Imaizumi M, Kim HJ, Zoghbi SS, Briard E, Hong J, Musachio JL, et al. PET imaging with [$^{11}$C]PBR28 can localize and quantify upregulated peripheral benzodiazepine receptors associated with cerebral ischemia in rat. Neurosci Lett 2007;411:200-5   DOI   ScienceOn
48 Kim SU, de Vellis J. Microglia in health and disease. J Neurosci Res 2005;81:302-13   DOI   ScienceOn
49 Sargsyan SA, Monk PN, Shaw PJ. Microglia as potential contributors to motor neuron injury in amyotrophic lateral sclerosis. Glia 2005;51:241-53   DOI   ScienceOn
50 Tai YF, Pavese N, Gerhard A, Tabrizi SJ, Barker RA, Brooks DJ, et al. Imaging microglial activation in Huntington's disease. Brain Res Bull 2007;72:148-51   DOI   ScienceOn