在中樞神經系統中，血清素器轉運體(SERT)濃度的變化與許多神經精神性異常疾病有關,例如憂鬱症、焦慮症、精神分裂、藥物濫用、酒癮、飲食失調、阿茲海默氏症(Alzheimer’s disease)及帕金森氏症(Parkinson’s disease)等。此外，它也是普遍使用的抗憂鬱處方藥物的主要作用標的。因此，以非侵入性的正子掃瞄 (Positron Emission Tomography, PET)或單光子射出電腦斷層攝影 (Single Photon Emission Computed Tomography, SPECT)活體造影技術探討血清素轉運器在腦部區域的分布將有助於探討血清素系統在神經精神性異常疾病的病理生理學及治療上所扮演的角色。本論文的總目標即為氟-18標誌血清素轉運器造影劑的發展與評估。近來，2-(2-amino-4-[18F] -fluorophenylthio)benzylamine ( 4-[18F] -ADAM )已被證實為具潛力的氟-18標誌血清素轉運器造影劑，並適用於動物及臨床前研究。然而，其低放化產率卻會妨礙其廣泛的應用性。因此，我們已發展一方法以改善其放化產率。此方法是基於分子軌域計算而推導出會發生親核性芳香環氟化反應之碳原子的電子電荷。基於計算所得結論，我們亦發展了一改良合成方法以製備4-[18F] –ADAM，並得到比之前所發表的合成方法更好的放化產率。而此計算方法也因此可作為一個預測親核性芳香環氟化反應發生位置的工具，並由結果證明此計算方法亦可以應用在其他系列的化合物上。
4-[18F]–ADAM更在大鼠及台灣彌猴體內以定量自動放射顯影術與microPET進一步地評估其是否為一具潛力的血清素轉運器造影劑。結果顯示4-[18F]–ADAM確實為一具潛力的氟-18標誌血清素轉運器造影劑。而由大鼠與台灣彌猴體內進行4-[18F]-ADAM的毒性與輻射劑量評估結果也發現4-[18F]–ADAM適合用於人體PET研究（在大鼠，單一劑量與五天連續劑量皆不會造成臨床上顯著的副作用。在猴子，大部分器官接受的輻射劑量介於7.1與35.7μGy/MBq之間，並且膀胱被視為是危急器官。）。在人體實驗中，研究結果顯示4-[18F]-ADAM PET在人腦中評估血清素轉運器狀態上為一個有用的工具。除了4-[18F]-ADAM之外，其一系列的同系物如[18F]-AFM, 2-[18F]-ADAM與4-[18F]-NMADAM也皆被合成，並在大鼠內評估其是否亦為具潛力的血清素轉運器造影劑。結果顯示[18F]-AFM為一有潛力的血清素轉運器造影劑，儘管其低放化產率(∼1%)也許會妨礙其應用性。相反地，2-[18F]-ADAM與4-[18F]-NMADAM則不是一個有潛力的血清素轉運器造影劑。

Alterations of serotonin transporters (SERT) densities have been implicated in a number of neuropsychiatric disorders, including major depression, anxiety disorders, schizophrenia, drug abuse, alcoholism, eating disorders, Alzheimer’s disease and Parkinson’s disease. In addition, it is also the primary target for widely prescribed antidepressant agents. Thus, in vivo imaging the regional brain distribution of SERT with Positron Emission Tomography (PET) or Single Photon Emission Computed Tomography (SPECT) will provide an important tool to study the role of the serotonergic system in the pathophysiology and treatment of neuropsychiatric disorders. The overall objective of this dissertation is to develop and evaluate the F-18 labelled SERT imaging agents. Recently, N,N-dimethyl -2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]-ADAM) has been proved to be a potent 18F-labelled SERT imaging agent and is suitable for animal and preclinical studies. However, its low radiochemical yield (RCY) has hampered its widespread use. Hence, we have developed a method to improve its RCY. The method is based on molecular orbital calculation to derive the electron charges on carbon atom at which the nucleophilic aromatic fluorination will occur. Based on this method, we have developed an improved method to prepare 4-[18F]-ADAM in a better yield than the one previously reported (15% v.s. 6%). The calculation method thus has been used as a tool to predict the position of nucleophilic aromatic fluorination and the results show it is applicable to other class of compounds.
4-[18F]-ADAM was further characterized in rats and Formosa Rock monkeys as a potential SERT imaging agent with autoradiography and microPET. The results show 4-[18F]-ADAM is indeed a potent F-18 labelled SERT imaging agent. Toxicity and radiation dosimetry studies in rats and monkeys show that 4-[18F]-ADAM is suitable for use in human PET imaging studies (In the rats, neither the single dose nor the five daily doses of 4-[18F]-ADAM produced overt adverse effects clinically. In the monkeys, the radiation doses received by most organs ranged between 7.1 and 35.7 μGy/MBq, and the urinary bladder was considered to be the critical organ). Human studies show that 4-[18F]-ADAM PET may be a useful tool in assessing the status of SERT in human brain. In addition to 4-[18F]-ADAM, a series of its analogs, [18F]-AFM, 2-[18F]-ADAM and 4-[18F]-NMADAM were synthesized and evaluated in rats as potential SERT imaging agents. The results show that [18F]-AFM is also a potent SERT imaging agent although the low RCY (∼1%) may hamper its usage as a SERT imaging agent. In contrast, both 2-[18F]-ADAM and 4-[18F]-NMADAM are not potent SERT imaging agents.

Preface i
Acknowledgements ii
Table of Contents iii
English Abstract viii
Chinese Abstract x

Chapter 1 Introduction 1
1.1 Serotonin 1
1.2 The Serotonergic System in the Brain 6
1.3 The Serotonin Receptors 9
1.4 The Serotonin Transporters (SERT) 14
1.4.1 Distribution of SERT in Human 14
1.4.2 Putative Structure of the SERT 15
1.4.3 The Interaction between SERT and 5-HT receptors 19
1.4.4 Drug development for SERT 19
1.5 Positron-Emitting Radionuclides 22
1.5.1 Cyclotrons 26
1.5.2 Properties of Fluorine 30
1.5.3 Production of Fluorine-18 31
1.6 Development for PET and PET/CT 34
1.7 Synthesis of Fluorine-18 Labelled Radiotracers 39
1.7.1 Electrophilic [18F]Fluorination 39
1.7.2 Nucleophilic [18F]Fluorination 40
1.8 Requirements for an Ideal SERT Imaging Agent 50
1.9 PET Tracers for the Serotonin System 51
1.9.1 5-HT Receptor Radioligands 51
1.9.2 SERT Radioligands 56
1.10 Reference 71

Chapter 2 Improved Synthesis of 4-[18F]-ADAM 95
2.1 Abstract 95
2.2 Introduction 96
2.3 Materials and Methods 100
2.3.1 Chemicals and Equipments 100
2.3.2 2-(2-Nitro-4-aminophenylthio)benzoic acid (5) 101
2.3.3 N,N-Dimethyl-2-(2-nitro-4-aminophenylthio)benzamide (6). 101
2.3.4 N,N-Dimethyl-2-(2-nitro-4-N,N-dimethylaminophenyl thio)benzamide (7)102
2.3.5 N,N-Dimethyl-2-(2-nitro-4-trimethylammoniumtrifluoro
-methanesulfonylphenylthio)benzamide (8).102
2.3.6 Synthesis of 4-[18F]-ADAM (2) 103
2.3.7 Computational Method 104
2.4 Results 106
2.5 Discussion 108
2.6 Conclusion 113
2.7 Reference 114

Chapter 3 Toxicity and Radiation Dosimetry Studies of the Serotonin Transporter Radioligand 4-[18F]-ADAM in Rats and Monkeys 120
3.1 Abstract 120
3.2 Introduction 122
3.3 Materials and Methods 124
3.3.1 Acute Toxicity Studies of 4-fluoro-ADAM in Rats 124
3.3.2 Dosimetry Studies of 4-[18F]-ADAM in Monkeys 128
3.4 Results 133
3.4.1 Acute Toxicity of 4-F-ADAM in Rats 133
3.4.2 Biodistributions of 4-[18F]-ADAM in Monkeys 133
3.4.3 Absorbed Radiation-Dose Estimates 134
3.5 Discussion 141
3.6 Conclusion 148
3.7 Reference 149

Chapter 4 Comparative Studies of 4-[18F]-ADAM, [18F]-AFM, 2-[18F]-ADAM and 4-[18F]-MADAM as Serotonin Transporters Imaging Agents in Rats using MicroPET 157
4.1 Abstract 157
4.2 Introduction 158
4.3 Materials and Methods 161
4.3.1 Chemicals and Equipments 161
4.3.2 N,N-dimethyl-2-(2-amino-4-[18F]fluorophenylthio)
-benzylamine (4-[18F]-ADAM, 1a) and N,N-Dimethyl-2-(2-[18F]fluoro-4-aminophenylthio)benzylamine(2-[18F]-ADAM, 3a). 162
4.3.3 2-[[2-Amino-4-([18F]fluoromethyl)phenyl]thio]-N,N
-dimethylbenzene-methanamine ([18F]-AFM, 2a) 163
4.3.4 2-(4-bromo-2-nitrophenylthio)benzoic acid (9). 164
4.3.5 2-(4-bromo-2-nitrophenylthio)-N-methylbenzamide (10) 164
4.3.6 1-(2-(4-bromo-2-nitrophenylthio)phenyl)-N-methylmethanamine (11). 165
4.3.7 tert-butyl-2-(4-bromo-2-nitrophenylthio)benzyl(methyl)carbamate (12) 165
4.3.8 2-(4-fluoro-2-nitrophenylthio)benzoic acid (14) 166
4.3.9 2-(4-fluoro-2-nitrophenylthio)-N-methylbenzamide (15) 166
4.3.10 5-fluoro-2-(2-((methylamino)methyl)phenylthio)aniline (4) 167
4.3.11 N-monomethyl-2-(2-amino-4-[18F]fluorophenylthio)benzylamine (4-[18F]- NMADAM, 4a) 168
4.3.12 Measurement of Partition Coefficient for 2-[18F]-ADAM (3a)and 4-[18F]-NMADAM (4a) 169
4.3.13 Animal Preparation 169
4.3.14 MicroPET Imaging Protocol 170
4.3.15 Magnetic Resonance Imaging 170
4.3.16 Imaging Analysis 171
4.4 Results 172
4.4.1 Radiosynthesis and Lipophilicity Measurement of all Four Radioligands 172
4.4.2 Rat MicroPET Imaging 175
4.5 Discussion 183
4.6 Conclusion 187
4.7 Reference 188

Chapter 5 Perspectives 192
5.1 Perspectives 192
5.2 Reference 198
Appendix Publication List 200

Adam, M. J., 1982. A rapid, stereoselective, high yielding synthesis of 2-deoxy-2-fluoro-D-hexopyranoses: reaction of glycals with acetyl hypofluorite. J Chem Soc Chem Comm. 1982(13), 730-731.
Adayev, T., Ranasinghe, B. and Banerjee, P., 2005. Transmembrane signaling in the brain by serotonin, a key regulator of physiology and emotion. Biosci Rep. 25(5), 363-385.
Albanese, D., Landini, D. and Penso, M., 1998. Hydrated tetrabutylammonium fluoride as a powerful nucleophilic fluorinating agent. J. Org. Chem. 63(25), 9587-9589.
Ambrose, J., 1973. Computerized transverse axial scanning (tomography). 2. Clinical application. Br J Radiol. 46(552), 1023-1047.
Ametamey, S. M. and Schubiger, P. A., 2006. PET radiopharmaceuticals for neuroreceptor imaging. Nuclear Science and Techniques. 17(3), 143-147.
Anderson, C. D., 1933a. Cosmic-Ray Positive and Negative Electrons. Phys Rev B Condens Matter. 44(5), 406-416.
Anderson, C. D., 1933b. The positive electron. Phys. Rev. 43(6), 491-494.
Angelini, G., Speranza, M., Wolf, A. P. and Shiue, C. Y., 1985. Nucleophilic aromatic substitution of activated cationic groups by 18F-labeled fluoride. A useful route to no-carrier-added(NCA) 18F-labeled aryl fluorides. J Fluorine Chem. 27(2), 177-191.
Ase, A. R., Reader, T. A., Hen, R., Riad, M. and Descarries, L., 2001. Regional changes in density of serotonin transporter in the brain of 5-HT1A and 5-HT1B knockout mice, and of serotonin innervation in the 5-HT1B knockout. J Neurochem. 78(3), 619-630.
Aznavour, N. and Zimmer, L., 2007. [18F] MPPF as a tool for the in vivo imaging of 5-HT1A receptors in animal and human brain. Neuropharmacology. 52(3), 695-707.
Bailer, U. F., Frank, G. K., Henry, S. E., Price, J. C., Meltzer, C. C., Mathis, C. A., Wagner, A., Thornton, L., Hoge, J. and Ziolko, S. K., 2007. Exaggerated 5-HT1A but normal 5-HT2A receptor activity in individuals ill with anorexia nervosa. Biol Psychiatry. 61(9), 1090-1099.
Bailey, D. L., Karp, J. S. and Surti, S., 2005. Physics and Instrumentation in PET. In: D. L. Bailey, D. W. Townsend, P. E. Valk and M. M.N. (Eds.). Positron Emission Tomography: Basic Sciences. Springer London, London, pp. 13-39.
Balkovetz, D. F., Tiruppathi, C., Leibach, F. H., Mahesh, V. B. and Ganapathy, V., 1989. Evidence for an imipramine-sensitive serotonin transporter in human placental brush-border membranes. J Biol Chem. 264(4), 2195-2198.
Blakely, R. D., Berson, H. E., Fremeau, R. T., Caron, M. G., Peek, M. M., Prince, H. K. and Bradley, C. C., 1991. Cloning and expression of a functional serotonin transporter from rat brain. Nature. 354(6348), 66-70.
Bockaert, J., Claeysen, S., Becamel, C., Dumuis, A. and Marin, P., 2006. Neuronal 5-HT metabotropic receptors: fine-tuning of their structure, signaling, and roles in synaptic modulation. Cell Tissue Res. 326(2), 553-572.
Brust, P., Zessin, J., Kuwabara, H., Pawelke, B., Kretzschmar, M., Hinz, R., Bergman, J., Eskola, O., Solin, O. and Steinbach, J., 2003. Positron emission tomography imaging of the serotonin transporter in the pig brain using [11C](+)-McN5652 and S-([18F] fluoromethyl)-(+)-McN5652. Synapse 47(2), 143-151.
Buck, A., Gucker, P. M., Schonbachler, R. D., Arigoni, M., Kneifel, S., Vollenweider, F. X., Ametamey, S. M. and Burger, C., 2000. Evaluation of serotonergic transporters using PET and [11C](+)McN-5652: assessment of methods. J Cereb Blood Flow Metab. 20(2), 253-262.
Cai, L., Lu, S. and Pike, V. W., 2008. Chemistry with [18F] Fluoride Ion. Eur. J. Org. Chem. 2008(17), 2853-2873.
Casella, V., Ido, T., Wolf, A. P., Fowler, J. S., MacGegor, R. R. and Ruth, T. J., 1980. Anhydrous F-18 labeled eslemental flurine for radiopharmaceutical preparation. J Nucl Med. 21(8), 750-757.
Chambers, R. D., 2004. Fluorine in organic chemistry. Oxford, Blackwell.
Cirillo, P., Golino, P., Ragni, M., Battaglia, C., Pacifico, F., Formisano, S., Buono, C., Condorelli, M. and Chiariello, M., 1999. Activated platelets and leucocytes cooperatively stimulate smooth muscle cell proliferation and proto-oncogene expression via release of soluble growth factors. Cardiovascular Res. 43(1), 210-218.
Clark, M. S., Lanigan, T. M., Page, N. M. and Russo, A. F., 1995. Induction of a serotonergic and neuronal phenotype in thyroid C-cells. J Neurosci 15(9), 6167-6178.
Cockcroft, J. D. and Walton, E. T. S., 1930. Experiments with High Velocity Positive Ions. Proc Roy Soc A. 129(811), 477-489.
Cockcroft, J. D. and Walton, E. T. S., 1932. Experiments with High Velocity Positive Ions. II. The Disintegration of Elements by High Velocity Protons. Proc Roy Soc A. 137(831), 229-242.
Coenen, H. H., Schuller, M., Stocklin, G., Klatte, B. and Knochel, A., 1986. Preparation of NCA [17-18F]-fluoroheptadecanoic acid in high yields via aminopolyether supported, nucleophilic fluorination. J Label Compd Radiopharm. 23(5), 455-467.
Coenen, H. H., 2007. Fluorine-18 Labeling Methods: Features and Possibilities of Basic Reactions. In: P. A. Schubiger, L. Lehmann and M. Friebe (Eds.). PET Chemistry: The Driving Force in Molecular Imaging. Springer, New York, pp. 15-40.
Constantinou, M., Aigbirhio, F. I., Smith, R. G., Ramsden, C. A. and Pike, V. W., 2001a. Xenon Difluoride Exchanges Fluoride under Mild Conditions: A Simple Preparation of [18F] Xenon Difluoride for PET and Mechanistic Studies. J. Am. Chem. Soc. 123(8), 1780-1781.
Constantinou, M., Shah, F. and Pike, V. W., 2001b. Radiofluoridations of m-substituted nitrobenzenes. J Labelled Compd Radiopharm 44 (Suppl.1), S889-S891.
Cooper, J. R., Bloom, F. E. and Roth, R. H., 1996. The biochemical basis of neuropharmacology. Oxford University Press, New York.
Cox, D. P., Terpinski, J. and Lawrynowicz, W., 1984. " Anhydrous" tetrabutylammonium fluoride: a mild but highly efficient source of nucleophilic fluoride ion. J Org Chem. 49(17), 3216-3219.
Craig, I. W., 2007. The importance of stress and genetic variation in human aggression. Bioessays. 29(3), 227-236.
Czernin, J., Allen-Auerbach, M. and Schelbert, H. R., 2007. Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006. J Nucl Med. 48(Suppl. 1), 78S-88S.
Dahlstrom, A. and Fuxe, K., 1964. Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol Scand Suppl. 62(Suppl. 232), 1-55.
Daws, L. C., Gould, G. G., Teicher, S. D., Gerhardt, G. A. and Frazer, A., 2000. 5-HT1B Receptor-Mediated Regulation of Serotonin Clearance in Rat Hippocampus In Vivo. J Neurochem. 75(5), 2113-2122.
Dinoiu, V., 2007. Chemical Fluorination of Organic Compounds. Revue Roumaine de Chimie. 52(3), 219-234.
Dirac, P. A. M., 1928a. The Quantum Theory of the Electron. Part II. Proc. R. Soc. Lond. A. 118(779), 351-361.
Dirac, P. A. M., 1928b. The quantum theory of the electron. Proc. R. Soc. Lond. A. 117(778), 610-624.
Djavadian, R. L., 2004. Serotonin and neurogenesis in the hippocampal dentate gyrus of adult mammals. Acta Neurobiol Exp. 64(2), 189-202.
Dolbier, W. R., 2005. Fluorine chemistry at the millennium. J. Fluorine Chem. 126(2), 157-163.
Ehrenkaufer, R. E. and MacGregor, R. R., 1982. F-18 perchloryl fluoride: synthesis and reactions. Name: J. Labelled Compd. Radiopharm. 19, 1637-1638.
Ehrlich, P., 1907. Chemotherapeutische Trypanosomen-Studien. Berliner klinische Wochenschrift. 11, 301-314.
Elliott, T. R., 1904. On the action of adrenaline. J Physiol Lond. 31, xx–xxi.
Fabre, V., Beaufour, C., Evrard, A., Rioux, A., Hanoun, N., Lesch, K. P., Murphy, D. L., Lanfumey, L., Hamon, M. and Martres, M. P., 2000. Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter. Eur J Neurosci. 12(7), 2299-2310.
Fang, P., Shiue, G. G., Shimazu, T., Greenberg, J. H. and Shiue, C. Y., 2004. Synthesis and evaluation of N,N-dimethyl-2-(2-amino-5-[18F]fluorophenylthio)benzylamine (5-[18F]-ADAM) as a serotonin transporter imaging agent. Appl Radiat Isot. 61(6), 1247-1254.
Faraj, B. A., Olkowski, Z. L. and Jackson, R. T., 1997. Prevalence of high serotonin uptake in lymphocytes of abstinent alcoholics. Biochem Pharmacol. 53(1), 53-57.
Ferris, R. M., Brieaddy, L., Mehta, N., Hollingsworth, E., Rigdon, G., Wang, C., Soroko, F., Wastila, W. and Cooper, B., 1995. Pharmacological properties of 403U76, a new chemical class of 5-hydroxytryptamine- and noradrenaline-reuptake inhibitor. J Pharm Pharmacol. 47(9), 775-781.
Fowler, J. S., Shiue, C. Y., Wolf, A. P., Salvadori, P. A. and MacGregor, R. R., 1982. l8F-1abeled acetyl hypofluorite for radiotracer synthesis. J Labell Compds Radiopharm. 19, 1634-1636.
Fowler, J. S. and Wolf, A. P., 1986. Positron emitter-labeled compounds: priorities and problems. In: M. E. Phelps, J. C. Mazziotta and H. R. Schelbert (Eds.). Positron Emission Tomography and Autoradiography: Principles and Applications for the Brain and Heart. Raven Press, New York, pp. 391-450.
Frankle, W. G., Huang, Y., Hwang, D. R., Talbot, P. S., Slifstein, M., Van Heertum, R., Abi-Dargham, A. and Laruelle, M., 2004. Comparative evaluation of serotonin transporter radioligands 11C-DASB and 11C-McN 5652 in healthy humans. J Nucl Med. 45(4), 682-694.
Gaddum, J. H. and Picarelli, Z. P., 1957. Two kinds of tryptamine receptor. Br J Pharmacol Chemother. 12(3), 323-328.
Gaspar, P., Cases, O. and Maroteaux, L., 2003. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci. 4(12), 1002-1012.
Ginovart, N., Wilson, A. A., Meyer, J. H., Hussey, D. and Houle, S., 2001. Positron emission tomography quantification of [11C]-DASB binding to the human serotonin transporter: modeling strategies. J Cereb Blood Flow Metab. 21(11), 1342-1353.
Goddard, A. W., Shekhar, A., Whiteman, A. F. and McDougle, C. J., 2008. Serotoninergic mechanisms in the treatment of obsessive–compulsive disorder. Drug Discov Today. 13(7-8), 325-332.
Griffiths, D. J., 2005. Introduction to Quantum Mechanics. Prentice Hall, New Jersey.
Guo, N., Alagille, D., Tamagnan, G., Price, R. R. and Baldwin, R. M., 2008. Microwave-induced nucleophilic [18F] fluorination on aromatic rings: Synthesis and effect of halogen on [18F] fluoride substitution of meta-halo (F, Cl, Br, I)-benzonitrile derivatives. Appl Radiat Isot. 66(10), 1396-1402.
Hahn, M. K. and Blakely, R. D., 2002. Monoamine transporter gene structure and polymorphisms in relation to psychiatric and other complex disorders. Pharmacogenomics J. 2(4), 217-235.
Hainer, V., Kabrnova, K., Aldhoon, B., Kunesova, M. and Wagenknecht, M., 2006. Serotonin and norepinephrine reuptake inhibition and eating behavior. Ann N Y Acad Sci. 1083, 252-269.
Halaris, A., 2003. Neurochemical aspects of the sexual response cycle. CNS Spectr. 8(3), 211-216.
Halford, J. C., Harrold, J. A., Lawton, C. L. and Blundell, J. E., 2005. Serotonin (5-HT) drugs: effects on appetite expression and use for the treatment of obesity. Curr Drug Targets. 6(2), 201-213.
Halldin, C., Gulyas, B., Langer, O. and Farde, L., 2001. Brain radioligands--state of the art and new trends. Q J Nucl Med. 45(2), 139-152.
Halldin, C., Lundberg, J., Tarkiainen, J., Hiltunen, J., Sovago, J., Gulyas, B., Guilloteau, D., Emond, P., Chalon, S., Vercouille, J. and Farde, L., 2003. A PET-examination of [11C]DADAM in human brain-A PET radioligand for the serotonin transporter with a fast equilibrium. J Nucl Med. 44, 68P.
Hariri, A. R. and Holmes, A., 2006. Genetics of emotional regulation: the role of the serotonin transporter in neural function. Trends Cogn Sci. 10(4), 182-191.
Heinz, A., Mann, K., Weinberger, D. R. and Goldman, D., 2001. Serotonergic Dysfunction, Negative Mood States, and Response to Alcohol. Alcohol Clin Exp Res. 25(4), 487-495.
Hensler, J. G., 2006. Serotonergic modulation of the limbic system. Neurosci Biobehav Rev. 30(2), 203-214.
Herth, M. M., Piel, M., Debus, F., Schmitt, U., Luddens, H. and Rosch, F., 2009. Preliminary in vivo and ex vivo evaluation of the 5-HT2A imaging probe [18F]MH.MZ. Nucl Med Biol. 36(4), 447-454.
Hiller, A., Fischer, C., Jordanova, A., Patt, J. T. and Steinbach, J., 2008. Investigations to the synthesis of nca [18F] FClO3 as electrophilic fluorinating agent. Appl Radiat Isot. 66(2), 152-157.
Hoffman, B. J., Mezey, E. and Brownstein, M. J., 1991. Cloning of a serotonin transporter affected by antidepressants. Science. 254(5031), 579-580.
Hoffman, E. J., Phelps, M. E., Mullani, N. A., Higgins, C. S. and Ter-Pogossian, M. M., 1976. Design and performance characteristics of a whole-body positron transaxial tomograph. J Nucl Med. 17(6), 493-502.
Houle, S., Ginovart, N., Hussey, D., Meyer, J. H. and Wilson, A. A., 2000. Imaging the serotonin transporter with positron emission tomography: initial human studies with [11C]DAPP and [11C]DASB. Eur J Nucl Med. 27(11), 1719-1722.
Hounsfield, G. N., 1973. Computerized transverse axial scanning (tomography): Part 1. Description of system. Br J Radiol. 46(552), 1016-1022.
Hoyer, D., Hannon, J. P. and Martin, G. R., 2002. Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav. 71(4), 533-554.
Huang, W. S., Huang, S. Y., Yeh, C. B., Ma, K. H., Wang, H. S., Peng, C. J. and Shiue, C. Y., 2007. 18F-ADAM PET in healthy and drug-na□ve depressant subjects. J Nucl Med. 48 (Suppl. 2), 261P.
Huang, W. S., Huang, S. Y., Yen, C. B., Liu, R. S., Wang, S. T. and Shiue, C. Y., 2009. Serotonin Transporters Binding in Healthy Controls and Drug-Na□ve Depressed Subjects: A Preliminary PET Study with 4-[18F]-ADAM. J Nucl Med, Sumitted.
Huang, Y., Bae, S. A., Zhu, Z., Guo, N., Hwang, D. R., Sudo, Y., Ngo, K., Kegeles, L. and Laruelle, M., 2001. Synthesis and characterization of a new PET ligand for the serotonin transporter: 11C-5-bromo-2-{2-[(dimethylamino)methyl]phenylsulfanyl} -phenylamine. J Nucl Med. 42, 112P.
Huang, Y., Hwang, D. R., Narendran, R., Sudo, Y., Chatterjee, R., Bae, S. A., Mawlawi, O., Kegeles, L. S., Wilson, A. A., Kung, H. F. and Laruelle, M., 2002. Comparative evaluation in nonhuman primates of five PET radiotracers for imaging the serotonin transporters: [11C]McN 5652, [11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM. J Cereb Blood Flow Metab. 22(11), 1377-1398.
Huang, Y., Zhu, Z., Narendran, R., Guo, N., Hwang, D. R., Phan, V., Talbot, P. S. and Laruelle, M., 2003. Preparation and pharmacological characterization of [18F]AFE as a new PET radiotracer for the serotonin transporters: Comparison with [18F]AFM. J Nucl Med. 44, 293P.
Huang, Y., Hwang, D. R., Bae, S. A., Sudo, Y., Guo, N., Zhu, Z., Narendran, R. and Laruelle, M., 2004a. A new positron emission tomography imaging agent for the serotonin transporter: synthesis, pharmacological characterization, and kinetic analysis of [11C]2-[2-(dimethylaminomethyl)phenylthio]-5-fluoromethylphenylamine ([11C]AFM). Nucl Med Biol. 31(5), 543-556.
Huang, Y., Narendran, R., Bae, S. A., Erritzoe, D., Guo, N., Zhu, Z., Hwang, D. R. and Laruelle, M., 2004b. A PET imaging agent with fast kinetics: synthesis and in vivo evaluation of the serotonin transporter ligand [11C]2-[2-dimethylaminomethylphenylthio)]-5-fluorophenylamine ([11C]AFA). Nucl Med Biol. 31(6), 727-738.
Huang, Y., Bae, S. A., Zhu, Z., Guo, N., Roth, B. L. and Laruelle, M., 2005. Fluorinated diaryl sulfides as serotonin transporter ligands: synthesis, structure-activity relationship study, and in vivo evaluation of fluorine-18-labeled compounds as PET imaging agents. J Med Chem. 48(7), 2559-2570.
Huang, Y., Zhu, Z., Narendran, R., Guo, N., Hwang, D.R., Phan, V., Talbot, P.S. and Laruelle, M., 2003. Preparation and pharmacological characterization of [18F]AFE as a new PET radiotracer for the serotonin transporters: Comparison with [18F]AFM. J. Nucl. Med. 44, 293P.
Huang, Y. Y., Huang, W. S., Chu, T. C. and Shiue, C. Y., 2009a. An improved synthesis of 4-[18F]-ADAM,a potent serotonin transporter imaging agent. Appl. Radiat. Isot. 67(6), 1063-1067.
Huang, Y. Y., Ma, K. H., Tseng, T. W., Chou, T. K., Ng, H., Mirsalis, J. C., Fu, Y. K., Chu, T. C., Huang, W. S. and Shiue, C. Y., 2009b. Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[18F]-ADAM in rats and monkeys Eur J Nucl Med Mol Imaging, In Press.
IAEA, 2006. Directory of cyclotrons used for radionuclide production in Member States 2006 Update
IAEA-DCRP/2006, Vienna (Austria).
Ichimiya, T., Suhara, T., Sudo, Y., Okubo, Y., Nakayama, K., Nankai, M., Inoue, M., Yasuno, F., Takano, A., Maeda, J. and Shibuya, H., 2002. Serotonin transporter binding in patients with mood disorders: a PET study with [11C](+)McN5652. Biol Psychiatry. 51(9), 715-722.
Jarkas, N., McConathy, J., Ely, T., Kilts, C. D., Votaw, J. and Goodman, M. M., 2001. Synthesis and radiolabeling of new derivatives of ADAM. Potential candidates as SERT imaging agents for PET. J Labelled Cpd. Radiopharm. 44 (Suppl. 1), S204-S206.
Jarkas, N., McConathy, J., Malveaux, E. J., Williams, L. A., Votaw, J. R., Kilts, C. D. and Goodman, M. M., 2003. Synthesis, characterization and microPET imaging of serotonin transporters (SERT) with [11C]HOMADAM: A new diarylsulfides SERT PET imaging agent. J Nucl Med. 44(Suppl. 1), 48P.
Jayanthi, L. D., Samuvel, D. J., Buck, E. R., Reith, M. E. and Ramamoorthy, S., Eds. (2007). Regulation of biogenic amine transporters. Handbook of Neurochemistry and Molecular Neurobiology: Neural Membranes and Transport. New York, Springer Science & Business Media.
Jilek, J., Sindelar, K., Pomykacek, J., Kmonicek, V., Sedivy, Z., Hrubantova, M., Holubek, J., Svatek, E., Ryska, M. and Koruna, I., 1989. Potential antidepressants: 2-(methoxy- and hydroxy-phenylthio)benzylamines as selective inhibitors of 5-hydroxytryptamine re-uptake in the brain. Collection of Czechoslovak chemical communications. 54(12), 3294-3338.
Johnson, B. A., 2004. Role of the serotonergic system in the neurobiology of alcoholism: implications for treatment. CNS drugs. 18(15), 1105-1118.
Kalia, M., 2006. Neurobiology of sleep. Metabolism. 55(10 Suppl 2), S2-S6.
Kandel, E. R., Schwartz, J. H. and Jessell, T. M., 2000. Principles of neural science. McGraw-Hill, New York.
Kiesewetter, D. O., Eckelman, W. C., Cohen, R. M., Finn, R. D. and Larson, S. M., 1986. Syntheses and D2 receptor affinities of derivatives of spiperone containing aliphatic halogens. Int J Rad Appl Instrum A. 37(12), 1181-1188.
Kilbourn, M. R., Hood, J. T. and Welch, M. J., 1984. A simple 18O water target for 18F production. Appl Radiat Isot. 35(7), 599-602.
Kilbourn, M. R., Jerabek, P. A. and Welch, M. J., 1985. An improved [18O] water target for [18F] fluoride production. Appl Radiat Isot. 36(4), 327-328.
Kilbourn, M. R., 1990. Fluorine-18 Labeling of Radiopharmaceuticals. National Academy Press, Washington, DC,.
Kim, D. W., Ahn, D. S., Oh, Y. H., Lee, S., Kil, H. S., Oh, S. J., Lee, S. J., Kim, J. S., Ryu, J. S. and Moon, D. H., 2006. A New Class of SN2 Reactions Catalyzed by Protic Solvents: Facile Fluorination for Isotopic Labeling of Diagnostic Molecules. J. Am. Chem. Soc. 128(50), 16394-16397.
Kim, D. W., Jeong, H. J., Lim, S. T., Sohn, M. H., Katzenellenbogen, J. A. and Chi, D. Y., 2008. Facile Nucleophilic Fluorination Reactions Using tert-Alcohols as a Reaction Medium: Significantly Enhanced Reactivity of Alkali Metal Fluorides and Improved Selectivity. J. Org. Chem. 73(3), 957-962.
Kish, S. J., Tong, J., Hornykiewicz, O., Rajput, A., Chang, L. J., Guttman, M. and Furukawa, Y., 2008. Preferential loss of serotonin markers in caudate versus putamen in Parkinson's disease. Brain. 131(Pt 1), 120-131.
Koskela, A. (2008). The brain serotonin transporter binding in young adults; methodological considerations and association with bulimia nervosa and acquired obesity. Department of Clinical Physiology and Nuclear Medicine. Helsinki, Finland, Helsinki University. Ph.D: 10-33.
Kretzschmar, M., Brust, P., Zessin, J., Cumming, P., Bergmann, R. and Johannsen, B., 2003. Autoradiographic imaging of the serotonin transporter in the brain of rats and pigs using S-([18F] fluoromethyl)-(+)-McN5652. Eur Neuropsychopharmacol. 13(5), 387-397.
Kuhar, M. J., Roth, R. H. and Aghajanian, G. K., 1972. Synaptosomes from forebrains of rats with midbrain raphe lesions: selective reduction of serotonin uptake. J Pharmacol Exp Ther. 181(1), 36-45.
Kumar, J. S. and Mann, J. J., 2007. PET tracers for 5-HT1A receptors and uses thereof. Drug Discov Today. 12(17-18), 748-56.
Langer, S. Z., Ed. (1987). Presynaptic regulation of monoaminergic neurons. Psychopharmacology: The third generation of progress. New York, Raven Press.
Laruelle, M., Slifstein, M. and Huang, Y., 2002. Positron emission tomography: imaging and quantification of neurotransporter availability. Methods. 27(3), 287-299.
Lawrence, E. O. and Edlefsen, N. E., 1930. On the production of high speed protons. Science. 72(3), 376-377.
Lawrence, E. O. and Livingston, M. S., 1931. The production of high speed protons without the use of high voltages. Phys Rev. 38(4), 834-834.
Lawrence, E. O. and Livingston, M. S., 1932. The production of high speed light ions without the use of high voltages. Phys Rev. 40(1), 19-35.
Lazarova, N., Simeon, F. G., Musachio, J. L., Lu, S. and Pike, V. W., 2007. Integration of a microwave reactor with synthia to provide a fully automated radiofluorination module. J. Label. Compd. Radiopharm. 50(5-6), 463-465.
Leonardo, E. D. and Hen, R., 2006. Genetics of affective and anxiety disorders. Annu Rev Psychol. 57, 117-137.
Lesch, K. P., Wolozin, B. L., Murphy, D. L. and Riederer, P., 1993. Primary structure of the human platelet serotonin uptake site: identity with the brain serotonin transporter. J Neurochem. 60(6), 2319-2322.
Lesch, K. P., Balling, U., Gross, J., Strauss, K., Wolozin, B. L., Murphy, D. L. and Riederer, P., 1994. Organization of the human serotonin transporter gene. J Neural Transm Gen Sect. 95(2), 157-162.
Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Muller, C. R., Hamer, D. H. and Murphy, D. L., 1996. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 274(5292), 1527-1531.
Li, I. H., Huang, W. S., Shiue, C. Y., Huang, Y. Y., Liu, R. S., Chyueh, S. C., Hu, S. H., Liao, M. H., Shen, L. H., Liu, J. C. and Ma, K. H., 2009. Study on the neuroprotective effect of fluoxetine against MDMA-induced neurotoxicity on the serotonin transporter in rat brain using micro-PET. NeuroImage, In Press.
Lide, D. R., 2002. CRC handbook of chemistry and physics. CRC press, Boca Raton, FL (USA).
Lopez-Munoz, F. and Alamo, C., 2009. Historical evolution of the neurotransmission concept. J Neural Transm. 116(5), 515-533.
Lundberg, J., Odano, I., Olsson, H., Halldin, C. and Farde, L., 2005. Quantification of 11C-MADAM binding to the serotonin transporter in the human brain. J. Nucl. Med. 46(9), 1505-1515.
Lundberg, J. (2006). PET studies of the serotonin transporter in the human brain. The department of clinical neuroscience. Stockholm, Sweden, Karolinska Institutet. Ph. D: 5.
Ma, K. H., Huang, W. S., Kuo, Y. Y., Peng, C. J., Liou, N. H., Liu, R. S., Hwang, J. J., Liu, J. C., Chen, H. J. and Shiue, C. Y., 2009. Validation of 4-[18F]-ADAM as a SERT imaging agent using micro-PET and autoradiography. Neuroimage. 45(3), 687-693.
Maes, M., Van Gastel, A., Delmeire, L. and Meltzer, H. Y., 1999. Decreased platelet alpha-2 adrenoceptor density in major depression: effects of tricyclic antidepressants and fluoxetine. Biol Psychiatry. 45(3), 278-284.
Marjam□ki, P., Zessin, J., Eskola, O., Gr□nroos, T., Haaparanta, M., Bergman, J., Lehikoinen, P., Forsback, S., Brust, P. and Steinbach, J., 2003. S-[18F] fluoromethyl -(+)-McN5652, a PET tracer for the serotonin transporter: evaluation in rats. Synapse 47(1), 45-53.
Marner, L., Gillings, N., Comley, R. A., Baare, W. F. C., Rabiner, E. A., Wilson, A. A., Houle, S., Hasselbalch, S. G., Svarer, C. and Gunn, R. N., 2009. Kinetic Modeling of 11C-SB207145 Binding to 5-HT4 Receptors in the Human Brain In Vivo. J Nucl Med. 50(6), 900-8.
Mason, N. S. and Mathis, C., 2005. Radiohalogens for PET imaging. In: D. L. Bailey, D. W. Townsend, P. E. Valk and M. M.N. (Eds.). Positron Emission Tomography:Basic Science Springer London, London, pp. 217-236.
Mawlawi, O. and Townsend, D. W., 2009. Multimodality imaging: an update on PET/CT technology. Eur J Nucl Med Mol Imaging. 36(Supp 1), S15-S29.
Meltzer, H. Y., Arora, R. C., Baber, R. and Tricou, B. J., 1981. Serotonin uptake in blood platelets of psychiatric patients. Arch Gen Psychiatry. 38(12), 1322-1326.
Meltzer, H. Y., Li, Z., Kaneda, Y. and Ichikawa, J., 2003. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 27(7), 1159-1172.
Meyer, J. H., Wilson, A. A., Ginovart, N., Goulding, V., Hussey, D., Hood, K. and Houle, S., 2001. Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [11C]DASB PET imaging study. Am J Psychiatry. 158(11), 1843-1849.
Michelsen, K. A., Prickaerts, J. and Steinbusch, H. W., 2008. The dorsal raphe nucleus and serotonin: implications for neuroplasticity linked to major depression and Alzheimer's disease. Prog Brain Res. 172, 233-264.
Miller, K. J. and Hoffman, B. J., 1994. Adenosine A3 receptors regulate serotonin transport via nitric oxide and cGMP. J Biol Chem. 269(44), 27351-27356.
Milton, B. F. (1995). Commercial compact cyclotrons in the 90's. International conference on cyclotrons and their applications, Cape Town (South Africa).
Muller, C. P., Carey, R. J., Huston, J. P. and De Souza Silva, M. A., 2007. Serotonin and psychostimulant addiction: focus on 5-HT1A-receptors. Prog Neurobiol. 81(3), 133-178.
Murphy, D. L., Wichems, C., Li, Q. and Heils, A., 1999. Molecular manipulations as tools for enhancing our understanding of 5-HT neurotransmission. Trends Pharmacol Sci. 20(6), 246-252.
Musselman, D. L., Marzec, U., Davidoff, M., Manatunga, A. K., Gao, F., Reemsnyder, A., Duggirala, S., Larsen, H., Taylor, R. W. and Hanson, S., 2002. Platelet activation and secretion in patients with major depression, thoracic aortic atherosclerosis, or renal dialysis treatment. Depress Anxiety. 15(3), 91-101.
Nabulsi, N., Williams, W., Planeta-Wilson, B., Labaree, D., Ropchan, J., Neumeister, A., Carson, R. and Huang, Y., 2008. The serotonin transporter tracer [11C] AFM provides high specific binding signals in humans. J Nucl Med. 49(Supp 1), 80P.
Nichols, D. E. and Nichols, C. D., 2008. Serotonin receptors. Chem Rev. 108(5), 1614-1641.
Nickles, R. J., Daube, M. E. and Ruth, T. J., 1984. An 18O2 target for the production of [18F] F2. Int J Appl Radiat Isot. 35, 117-122.
Nutt, R., 2002. The history of positron emission tomography. Mol Imaging Biol. 4(1), 11-26.
Nye, J. A., Votaw, J. R., Jarkas, N., Purselle, D., Camp, V., Bremner, J. D., Kilts, C. D., Nemeroff, C. B. and Goodman, M. M., 2008. Compartmental modeling of 11C-HOMADAM binding to the serotonin transporter in the healthy human brain. J Nucl Med. 49(12), 2018-2025.
Oh, Y. H., Ahn, D. S., Chung, S. Y., Jeon, J. H., Park, S. W., Oh, S. J., Kim, D. W., Kil, H. S., Chi, D. Y. and Lee, S., 2007. Facile SN2 Reaction in Protic Solvent: Quantum Chemical Analysis. J. Phys. Chem. A. 111(40), 10152-10161.
Owens, M. J. and Nemeroff, C. B., 1994. Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem. 40(2), 288-295.
Oya, S., Choi, S. R., Hou, C., Kung, M. P., Acton, P. D., Shiue, C. Y. and Kung, H. F., 2001. Synthesis and characterization of 18F-IDAM as a PET imaging agent for serotonin transporters. J. Labelled Cpd. Radiopharm. 44 (Suppl. 1), S15-S17.
Oya, S., Choi, S. R., Coenen, H. and Kung, H. F., 2002. New PET imaging agent for the serotonin transporter: [18F]ACF (2-[(2-amino-4-chloro-5-fluorophenyl)thio]-N,N-dimethyl-benzenmethanamine). J Med Chem. 45(21), 4716-4723.
Paans, A. M. J., 2003. Compact cyclotrons for the production of tracers and radiopharmaceuticals. NUKLEONIKA. 48(Suppl. 2), S169-S172.
Pardo, C. A. and Eberhart, C. G., 2007. The neurobiology of autism. Brain Pathol. 17(4), 434-447.
Parsey, R. V., Kegeles, L. S., Hwang, D. R., Simpson, N., Abi-Dargham, A., Mawlawi, O., Slifstein, M., Van Heertum, R. L., Mann, J. J. and Laruelle, M., 2000. In vivo quantification of brain serotonin transporters in humans using [11C]McN 5652. J Nucl Med. 41(9), 1465-1477.
Peng, C. J., Huang, Y. Y., Huang, W. S. and Shiue, C. Y., 2008. An automated synthesis of N, N-dimethyl-2-(2-amino-4-[18F] fluorophenylthio) benzylamine (4-[18F]-ADAM) for imaging serotonin transporters. Appl Radiat Isot. 66(5), 625-631.
Perkins, A. C. and Frier, M., 2004. Radionuclide imaging in drug development. Curr Pharm Des. 10(24), 2907-2921.
Phelps, M. E., Hoffman, E. J., Mullani, N. A. and Ter-Pogossian, M. M., 1975. Application of annihilation coincidence detection to transaxial reconstruction tomography. J Nucl Med. 16(3), 210-224.
Phelps, M. E., Hoffman, E. J., Mullani, N. A. and Higgins, C. S., 1976. Design considerations for a positron emission transaxial tomograph (PETT III). IEEE Tran Nucl Sci. 23(1), 516-522.
Pierson, M. E., Andersson, J., Nyberg, S., McCarthy, D. J., Finnema, S. J., Varnas, K., Takano, A., Karlsson, P., Gulyas, B. and Medd, A. M., 2008. [11C] AZ10419369: A selective 5-HT1B receptor radioligand suitable for positron emission tomography (PET). Characterization in the primate brain. NeuroImage. 41(3), 1075-1085.
Plenge, P., Mellerup, E. T. and Laursen, H., 1990. Regional distribution of the serotonin transport complex in human brain, identified with 3H-paroxetine, 3H-citalopram and 3H-imipramine. Prog Neuropsychopharmacol Biol Psychiatry. 14(1), 61-72.
Popova, N. K., 2006. From genes to aggressive behavior: the role of serotonergic system. Bioessays. 28(5), 495-503.
Qaim, S. M., Clark, J. C., Crouzel, C., Guillaume, M., Helmeke, H. J., Nebeling, B., Pike, V. W. and Stocklin, G., 1993. PET radionuclide production. In: G. Stocklin and V. W. Pike (Eds.). Radiopharmaceuticals for positron emission tomography. Kluwer Academic Publishers, Dordrecht, pp. 1-43.
Rang, H. P., Dale, M. M., Ritter, J. M. and Moore, P. K., 2003. How drugs act: molecular aspects. . In: H. P. Rang, M. M. Dale and J. M. Ritter (Eds.). Pharmacology. Harcourt Publishers Ltd, Edinburgh, UK, pp. 22-50.
Rang, H. P., Dale, M. M. and Ritter, J. M., Eds. (2007). Pharmacology. Edinburgh, United Kingdom, Churchill Livingstone.
Ressler, K. J. and Nemeroff, C. B., 2000. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety. 12(Suppl 1), 2-19.
Robertson, J. S., Marr, R. B., Rosenblum, M., Radeka, V. and Yamamoto, Y. L. (1973). 32-Crystal positron transverse section detector (15-16 September 1972). Tomographic Imaging in Nuclear Medicine New York, The Society of Nuclear Medicine.
Ross, S. B. and Renyl, A. L., 1967. Accumulation of tritiated 5-hydroxytryptamine in brain slices. Life Sci 6(13), 1407-1415.
Rudnick, G., 1977. Active transport of 5-hydroxytryptamine by plasma membrane vesicles isolated from human blood platelets. J Biol Chem. 252(7), 2170-2174.
Ruth, T. J., Buckley, K. R., Chun, K. S., Hurtado, E. T., Jivan, S. and Zeisler, S., 2001. A proof of principle for targetry to produce ultra high quantities of 18F-fluoride. Appl Radiat Isot. 55(4), 457-461.
Rutherford, E., 1919. Atomic projectiles and their collisions with light atoms. Science. 50(1299), 467-473.
Sandford, G., 2007. Elemental fluorine in organic chemistry (1997–2006). J Fluorine Chem. 128(2), 90-104.
Schrobilgen, G. J., Firnau, G., Chirakal, R. and Garnett, E. S., 1981. Synthesis of [18F] XeF2, a novel agent for the preparation of l8F radiopharmaceuticals. J. Chem. Soc. Chem. Comm, 198-199.
Schroeter, S., Levey, A. I. and Blakely, R. D., 1997. Polarized expression of the antidepressant-sensitive serotonin transporter in epinephrine-synthesizing chromaffin cells of the rat adrenal gland. Mol Cell Neurosci. 9(3), 170-184.
Shen, B., Loffler, D., Zeller, K. P., Ubele, M., Reischl, G. and Machulla, H. J., 2007. Decarbonylation of multi-substituted [18F] benzaldehydes for modelling syntheses of 18F-labelled aromatic amino acids. Appl Radiat Isot. 65(11), 1227-1231.
Shen, B., Loffler, D., Reischl, G., Machulla, H. J. and Zeller, K. P., 2008. Nucleophilic substitution of nitro groups by [18F] fluoride in methoxy-substituted ortho-nitrobenzaldehydes—A systematic study. J. Fluorine Chem. 130(2), 216-224.
Shiue, C. Y., 1983. A rapid synthesis of 2-deoxy-2-fluoro-D-glucose from xenon difluoride suitable for labeling with l8F. J Labelled Compd Radiopharm. 20, 157-162.
Shiue, C. Y., Fowler, J. S., Wolf, A. P., McPherson, D. W., Arnett, C. D. and Zecca, L., 1986. No-carrier-added fluorine-18-labeled N-methylspiroperidol: synthesis and biodistribution in mice. J Nucl Med. 27(2), 226-234.
Shiue, C. Y., Shiue, G. G., Mozley, P. D., Kung, M. P., Zhuang, Z. P., Kim, H. J. and Kung, H. F., 1997. p-[18F]-MPPF: a potential radioligand for PET studies of 5-HT1A receptors in humans. Synapse. 25(2), 147-154.
Shiue, C. Y., Shiue, G. G., Nowak, P. A., Oya, S., Choi, S. R. and Kung, H. F., 2000. 5-Iodo-2-{[2,2-[11C]dimethylamino)methyl]phenyl]thio}benzyl alcohol ([11C]IDAM): a new serotonin re-uptake sites tracer for PET studies. J Nucl Med. 41(Suupl), 241P.
Shiue, C. Y. and Welch, M. J., 2004. Update on PET radiopharmaceuticals: life beyond fluorodeoxyglucose. Radiol Clin North Am. 42(6), 1033-53.
Shiue, G. G., Fang, P. and Shiue, C. Y., 2003a. Synthesis of N,N-dimethyl-2-(2-amino-4 -[18F]fluorophenylthio)benzylamine as a serotonin transporter imaging agent. Appl Radiat Isot. 58(2), 183-191.
Shiue, G. G., Choi, S. R., Fang, P., Hou, C., Acton, P. D., Cardi, C., Saffer, J. R., Greenberg, J. H., Karp, J. S., Kung, H. F. and Shiue, C. Y., 2003b. N,N-dimethyl-2-(2 -amino-4-18F-fluorophenylthio)-benzylamine (4-[18F]-ADAM): an improved PET radioligand for serotonin transporters. J Nucl Med. 44(12), 1890-1897.
Siegel, G. J., Albers, R. W., Brady, S. and Price, D. L., 2005. Basic Neurochemistry: Molecular, cellular and medical aspects. In: (Eds.). Academic Press New York, pp. 227-248.
Singh, M. and Waluch, V., 2000. Physics and instrumentation for imaging in-vivo drug distribution. Adv Drug Deliv Rev. 41(1), 7-20.
Snell, A. H., 1937. Minutes of the Pasadena Meeting 1936: A new radioactive isotope of fluorine. Proceedings of the American Physical Society: Phys Rev. 51, 143.
Sood, S., Firnau, G. and Garnett, E. S., 1983. Radiofluorination with xenon difluoride: a new high yield synthesis of [18F] 2-fluro-2-deoxy-D-glucose. The International journal of applied radiation and isotopes. 34(4), 743-745.
Soret, M., Bacharach, S. L. and Buvat, I., 2007. Partial-volume effect in PET tumor imaging. J Nucl Med. 48(6), 932-945.
Stockmeier, C. A., Shapiro, L. A., Dilley, G. E., Kolli, T. N., Friedman, L. and Rajkowska, G., 1998. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression-postmortem evidence for decreased serotonin activity. J Neurosci. 18(18), 7394-7401.
Stockmeier, C. A., Shi, X., Konick, L., Overholser, J. C., Jurjus, G., Meltzer, H. Y., Friedman, L., Blier, P. and Rajkowska, G., 2002. Neurokinin-1 receptors are decreased in major depressive disorder. Neuroreport. 13(9), 1223-1227.
Suehiro, M., Ravert, H. T., Dannals, R. F., Scheffel, U. and Wagner, H. N., 1992. Synthesis of a radiotracer for studying serotonin uptake sites with positron emission tomography:[11C]McN-5652-Z. J Labelled Cpd. Radiopharm. 31(10), 841-848.
Suehiro, M., Greenberg, J. H., Shiue, C. Y., Gonzalez, C., Dembowski, B. and Reivich, M., 1996. Radiosynthesis and biodistribution of the S-[18F]fluoroethyl analog of McN5652. Nucl Med Biol. 23(4), 407-412.
Sun, H. and DiMagno, S. G., 2007. Competitive demethylation and substitution in N, N, N-trimethylanilinium fluorides. J. Fluoroine Chem. 128(7), 806-812.
Szabo, Z., Kao, P. F., Scheffel, U., Suehiro, M., Mathews, W. B., Ravert, H. T., Musachio, J. L., Marenco, S., Kim, S. E., Ricaurte, G. A. and et al., 1995. Positron emission tomography imaging of serotonin transporters in the human brain using [11C](+)McN5652. Synapse. 20(1), 37-43.
Szabo, Z., McCann, U. D., Wilson, A. A., Scheffel, U., Owonikoko, T., Mathews, W. B., Ravert, H. T., Hilton, J., Dannals, R. F. and Ricaurte, G. A., 2002. Comparison of (+)-11C-McN5652 and 11C-DASB as serotonin transporter radioligands under various experimental conditions. J Nucl Med. 43(5), 678-692.
Tamir, H., Hsiung, S. C., Liu, K. P., Blakely, R. D., Russo, A. F., Clark, M. S., Nunez, E. A. and Gershon, M. D., 1996. Expression and development of a functional plasmalemmal 5-hydroxytryptamine transporter by thyroid follicular cells. Endocrinology. 137(10), 4475-4486.
Tarkiainen, J., Vercouillie, J., Emond, P., Sandell, J., hiltunen, J., Frangin, Y., Guilloteau, D. and Halldin, C., 2001. Carbon-11 labelling of MADAM in two different positions: a highly selective PET radioligand for the serotonin transporter. J Labelled Cpd Radiopharm. 44(14), 1013-1023.
Tecott, L., Shtrom, S. and Julius, D., 1995. Expression of a serotonin-gated ion channel in embryonic neural and nonneural tissues. Mol Cell Neurosci. 6(1), 43-55.
Townsend, D. W., 2008. Multimodality imaging of structure and function. Phys. Med. Biol. 53(4), R1-R39.
Varnas, K., Nyberg, S., Halldin, C., Varrone, A., Takano, A., Karlsson, P., McCarthy, D., Smith, M., Pierson, M. E. and Soderstrom, J., 2008. Quantitative analyses of [11C] AZ10419369 binding to 5-HT1B receptors in the human brain. Neuroimage. 41, 104P.
Vercouillie, J., Tarkiainen, J., Halldin, C., Emond, P., Chalon, S., Sandell, J., Langer, O. and Guilloteau, D., 2001. Precursor synthesis and radiolabelling of [11C] ADAM: A potential radioligand for the serotonin transporter exploration by pet. Journal of labelled compounds & radiopharmaceuticals. 44(2), 113-120.
Vlasov, V. M., 2003. Nucleophilic substitution of the nitro group, fluorine and chlorine in aromatic compounds. Russ. Chem. Rev. 72(8), 681-703.
Wade, P. R., Chen, J., Jaffe, B., Kassem, I. S., Blakely, R. D. and Gershon, M. D., 1996. Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci. 16(7), 2352-2364.
Wagner, H. N., 1998. A brief history of Positron Emission Tomography (PET). Semin Nucl Med. 28(3), 213-220.
Wang, J. L., Parhi, A. K., Oya, S., Lieberman, B., Kung, M. P. and Kung, H. F., 2008. 2-(2'-((Dimethylamino) methyl)-4'-(3-[18F] fluoropropoxy)-phenylthio) benzenamine for positron emission tomography imaging of serotonin transporters. Nucl Med Biol. 35(4), 447-458.
Waterhouse, R. N., 2003. Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents. Mol Imaging Biol. 5(6), 376-389.
Welch, M. J. and Redvanly, C. S., 2003. Handbook of Radiopharmaceuticals. John Wiley & Sons Ltd, New York.
Wellsow, J., Kovar, K. A. and Machulla, H. J., 2002. Molecular modeling of potential new and selective PET radiotracers for the serotonin transporter. J Pharm Pharm Sci. 5(3), 245-257.
Whitaker-Azmitia, P. M., 1999. The discovery of serotonin and its role in neuroscience. NEUROPSYCHOPHARMACOLOGY. 21(2 Suppl), 2S-8S.
Wieland, B. W., Hendry, G. O., Schmidt, D. G., Bida, G. and Ruth, T. J., 1986. Efficient small-volume O-18 water targets for producing F-18 fluoride with low energy protons. J. Label. Compd. Radiopharm. 13, 1205-1207.
Wilson, A. A. and Houle, S., 1999. Radiosynthesis of Carbon-11 labelled N-methyl-2 -(arylthio) benzylamines: Potential radiotracers for the serotonin reuptake receptor. J Labelled Cpd. Radiopharm. 42(13), 1277-1288.
Wilson, A. A., Ginovart, N., Schmidt, M., Meyer, J. H., Threlkeld, P. G. and Houle, S., 2000. Novel radiotracers for imaging the serotonin transporter by positron emission tomography: synthesis, radiosynthesis, and in vitro and ex vivo evaluation of 11C-labeled 2-(phenylthio) araalkylamines. J Med Chem. 43(16), 3103-3110.
Wirz-Justice, A., 1988. Platelet research in psychiatry. Experientia. 44(2), 145-152.
Wong, D. T., Perry, K. W. and Bymaster, F. P., 2005. The discovery of fluoxetine hydrochloride (Prozac). Nat Rev Drug Discov. 4(9), 764-774.
Zahniser, N. R. and Doolen, S., 2001. Chronic and acute regulation of Na+/Cl–-dependent neurotransmitter transporters: drugs, substrates, presynaptic receptors, and signaling systems. Pharmacol Ther. 92(1), 21-55.
Zessin, J., Eskola, O., Brust, P., Bergman, J., Steinbach, J., Lehikoinen, P., Solin, O. and Johannsen, B., 2001. Synthesis of S-([18F]fluoromethyl)-(+)-McN5652 as a potential PET radioligand for the serotonin transporter. Nucl Med Biol. 28(7), 857-863.