PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives
<p>(<b>A</b>) Earlier PET radiotracers, [<sup>11</sup>C]Prazosin, [<sup>11</sup>C]Bunazosin, and [<sup>11</sup>C]GB67 for cardiac α1-AR imaging. (<b>B</b>) Antagonist PET radiotracers based on sertindole. (<b>C</b>) Antagonist PET radiotracers based on octoclothepin for brain α1-AR imaging.</p> "> Figure 2
<p>Various classes of α2-ARs antagonist radiotracers.</p> "> Figure 3
<p>Anti-depressive & antihypertensive based α2-AR PET radiotracers.</p> "> Figure 4
<p>Parametric maps of <b>16</b> in living porcine brain. (<b>A</b>) Baseline study using <b>16</b> showed regional differences in its distribution. (<b>B</b>) Blocking experiment (yohimbine at 0.07 mg/kg) reduced the scale of distribution volume (<span class="html-italic">V</span><sub>d</sub>) to ~2 mL g<sup>−1</sup> in all the α2-AR bound regions. (<b>C</b>) Increased dose of yohimbine (1.6 mg/kg) had no further significant effect in comparison to the low dose (<span class="html-italic">n</span> = 3) Maps are superimposed on the MR image. Adapted from JNM publication by Jacobsen S, Pedersen, K.; Smith, D.F.; Jensen, S.B.; Munk, O.L.; Cumming P [<a href="#B97-molecules-25-04017" class="html-bibr">97</a>]. Permission obtained from SNMMI.</p> "> Figure 5
<p>α2A-antagonist (<b>17</b>) and agonist (<b>18</b>) PET radiotracers.</p> "> Figure 6
<p>PET radiotracers for α2C-ARs.</p> "> Figure 7
<p>PET/CT images and time-activity curves of <b>21</b> for striatum and cerebellar cortex of (<b>A</b>) α2A KO (<b>B</b>) α2AC KO and (<b>C</b>) WT mice. Brain uptake of <b>21</b> in α2AC KO is negligible and is similar in α2A KO and WT mice with 7.8–8.1% ID/g at 1 min and 1.2% ID/g at 30 min after <b>21</b> injection. The striatum to cerebellar cortex radioactivity ratios (at 5–15 min) for α2AC KO mice did not differ and for α2A KO and WT mice are alike. Adapted from JNM publication by Arponen E.; Helin, S.; Marjamäki, P.; Grönroos, T.; Holm, P.; Löyttyniemi, E.; Någren, K.; Scheinin, M.; Haaparanta-Solin, M.; Sallinen, J.; [<a href="#B36-molecules-25-04017" class="html-bibr">36</a>]. Permission obtained from SNMMI.</p> "> Figure 8
<p>Early PET radiotracers for cerebral β-ARs.</p> "> Figure 9
<p>Radiotracers based on various β-AR blockers.</p> "> Figure 10
<p>Another set of latest β-AR PET radiotracers.</p> ">
Abstract
:1. Introduction
Receptor | Distribution | Distinct Functions and Associated Disorders | Ref | |
---|---|---|---|---|
α1 | α1A | High levels in olfactory system, hypothalamic nuclei, and brainstem. Moderate levels in amygdala, cerebral cortex, and cerebellum | Involved in neurotransmission of NE as well as γ-aminobutyric acid (GABA) and NMDA. May mediate effects of anti-depressants in treating depression and obsessive compulsive disorder (OCD) | [18,20,21,22,23,24] |
α1B | Thalamic nuclei, lateral nucleus of amygdala, cerebral cortex, some septal regions, brain stem regions | May play a role in behavioral activation. Associated with addiction, and neurodegenerative disorders (Multiple System Atrophy) | [18,20,21,24,25,26,27] | |
α1D | Olfactory bulb, cerebral cortex, hippocampus, reticular thalamic nuclei, and amygdala | Mediates changes in locomotor behaviors. Associated with stress. | [18,20,23,28,29] | |
α2 | α2A | Locus coeruleus, midbrain, hypothalamus, amygdala, cerebral cortex, and brain stem | Mediate functions of most of the α2-agonists used in sedation, antinociception, and behavioral actions. Associated with ADHD, anxiety | [18,23,30,31,32,33,34,35] |
α2B | Thalamus, hypothalamus, cerebellar Purkinje layer | Mediate antinociceptive action of nitrous oxide | [18,30,31] | |
α2C | Hippocampus, striatum, olfactory tubercle, medulla, and basal ganglia | Involved in the neuronal release of NE as well as dopamine and serotonin. Potential therapeutic targets in depression & schizophrenia | [18,30,31,36,37,38,39] | |
β | β1 | Homologous distribution. Expression was found (mostly β1 and β2) in frontal cortex, striatum, thalamus, putamen, amygdala, cerebellum, cerebral cortex and hippocampus. | Essential to motor learning, emotional memory storage and regulation of neuronal regeneration. Associated with mood disorders, aging, Alzheimer’s disease, Parkinson’s disease. | [16,18,40,41,42,43,44,45,46,47,48] |
β2 | ||||
β3 |
2. α1-AR PET Radiotracers
3. α2-AR Subtype and Nonspecific PET Radiotracers
3.1. α2A-Specific PET Radiotracers
3.2. α2C-Specific PET Radiotracers
4. β-ARs and Nonselective PET Radiotracers
5. Conclusions
Funding
Conflicts of Interest
References
- Scott, J.A. Positron Emission Tomography: Basic Science and Clinical Practice. Am. J. Roentgenol. 2004, 182, 418. [Google Scholar] [CrossRef]
- Shukla, A.; Kumar, U. Positron emission tomography: An overview. J. Med. Phys. 2006, 31, 13–21. [Google Scholar] [CrossRef] [PubMed]
- McCluskey, S.P.; Plisson, C.; Rabiner, E.A.; Howes, O. Advances in CNS PET: The state-of-the-art for new imaging targets for pathophysiology and drug development. Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 451–489. [Google Scholar] [CrossRef] [Green Version]
- Rankovic, Z. CNS Drug Design: Balancing Physicochemical Properties for Optimal Brain Exposure. J. Med. Chem. 2015, 58, 2584–2608. [Google Scholar] [CrossRef] [PubMed]
- Adenot, M.; Lahana, R. Blood-Brain Barrier Permeation Models: Discriminating between Potential CNS and Non-CNS Drugs Including P-Glycoprotein Substrates. J. Chem. Inf. Comput. Sci. 2004, 44, 239–248. [Google Scholar] [CrossRef]
- Agdeppa, E.D.; Spilker, M.E. A review of imaging agent development. AAPS J. 2009, 11, 286–299. [Google Scholar] [CrossRef]
- Kumar, J.S.; Mann, J. PET Tracers for Serotonin Receptors and Their Applications. Cent. Nerv. Syst. Agents Med. Chem. 2014, 14, 96–112. [Google Scholar] [CrossRef] [Green Version]
- Dunphy, M.P.S.; Lewis, J.S. Radiopharmaceuticals in preclinical and clinical development for monitoring of therapy with PET. J. Nucl. Med. 2009, 50, 106–122. [Google Scholar] [CrossRef] [Green Version]
- Sneader, W. The discovery and synthesis of epinephrine. Drug News Perspect. 2001, 14, 491–494. [Google Scholar] [CrossRef]
- Arthur, G. Epinephrine: A short history. Lancet Respir. Med. 2015, 3, 350–351. [Google Scholar] [CrossRef]
- Schmidt, K.T.; Weinshenker, D. Adrenaline rush: The role of adrenergic receptors in stimulant-induced behaviors. Mol. Pharmacol. 2014, 85, 640–650. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eisenhofer, G.; Kopin, I.J.; Goldstein, D.S. Catecholamine metabolism: A contemporary view with implications for physiology and medicine. Pharmacol. Rev. 2004, 56, 331–349. [Google Scholar] [CrossRef] [PubMed]
- Kirshner, N. Biosynthesis of adrenaline and noradrenaline. Pharmacol. Rev. 1959, 11, 350–357. [Google Scholar] [PubMed]
- Flatmark, T. Catecholamine biosynthesis and physiological regulation in neuroendocrine cells. Acta Physiol. Scand. 2000, 168, 1–17. [Google Scholar] [CrossRef] [PubMed]
- Ranjbar-Slamloo, Y.; Fazlali, Z. Dopamine and Noradrenaline in the Brain; Overlapping or Dissociate Functions? Front. Mol. Neurosci. 2020, 12, 1–8. [Google Scholar] [CrossRef] [Green Version]
- Strosberg, A.D. Structure, function, and regulation of adrenergic receptors. Protein Sci. 1993, 2, 1198–1209. [Google Scholar] [CrossRef] [Green Version]
- Ahlquist, R.P. A study of the adrenotropic receptors. Am. J. Physiol. 1948, 153, 586–600. [Google Scholar] [CrossRef]
- Philipp, M.; Hein, L. Adrenergic receptor knockout mice: Distinct functions of 9 receptor subtypes. Pharmacol. Ther. 2004, 101, 65–74. [Google Scholar] [CrossRef]
- Paul, J.; Bylund, B.; Lefkowitz, J.; Eikenburg, C.; Ruffolo, R.; Langer, Z.; Minneman, P. International Union of Pharmacology X. Recommendation for Nomenclature of adrenoreceptors: Consensus update. Am. Soc. Pharmacol. Exp. Ther. 1995, 47, 267–270. [Google Scholar]
- Day, H.E.W.; Campeau, S.; Watson, S.J.; Akil, H. Distribution of α(1a)-, α(1b)- and α(1d)-adrenergic receptor mRNA in the rat brain and spinal cord. J. Chem. Neuroanat. 1997, 13, 115–139. [Google Scholar] [CrossRef]
- Doze, V.A.; Handel, E.M.; Jensen, K.A.; Darsie, B.; Luger, E.J.; Haselton, J.R.; Talbot, J.N.; Rorabaugh, B.R. α1A- and α1B-adrenergic receptors differentially modulate antidepressant-like behavior in the mouse. Brain Res. 2009, 1285, 148–157. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Leslie, A. Characterization of a1-Adrenergic Receptor Subtypes in Rat Brain: A Reevaluation of [3H] WB41 04 and [3H] Prazosin Binding. Pharmacol. Exet. Am. Chem. Sciety Pharmacol. Experiemntal Ther. 1986, 29, 321–330. [Google Scholar]
- Reader, T.A.; Brière, R.; Grondin, L. Alpha-1 and alpha-2 adrenoceptor binding in cerebral cortex: Competition studies with [3H]prazosin and [3H]idazoxan. J. Neural Transm. 1987, 68, 79–95. [Google Scholar] [CrossRef] [PubMed]
- Drouin, C.; Darracq, L.; Trovero, F.; Blanc, G.; Glowinski, J.; Cotecchia, S.; Tassin, J.P. α1b-Adrenergic Receptors Control Locomotor and Rewarding Effects of Psychostimulants and Opiates. J. Neurosci. 2002, 22, 2873–2884. [Google Scholar] [CrossRef]
- Zuscik, M.J.; Sands, S.; Ross, S.A.; Waugh, D.J.J.; Gaivin, R.J.; Morilak, D.; Perez, D.M. Overexpression of the α(1B)-adrenergic receptor causes apoptotic neurodegeneration: Multiple system atrophy. Nat. Med. 2000, 6, 1388–1394. [Google Scholar] [CrossRef]
- Hayashi, R.; Ohmori, E.; Isogaya, M.; Moriwaki, M.; Kumagai, H. Design and synthesis of selective α1B adrenoceptor antagonists. Bioorg. Med. Chem. Lett. 2006, 16, 4045–4047. [Google Scholar] [CrossRef]
- Spreng, M.; Cotecchia, S.; Schenk, F. A behavioral study of alpha-1b adrenergic receptor knockout mice: Increased reaction to novelty and selectively reduced learning capacities. Neurobiol. Learn. Mem. 2001, 75, 214–229. [Google Scholar] [CrossRef] [Green Version]
- Sadalge, A.; Coughlin, L.; Fu, H.; Wang, B.; Valladares, O.; Valentino, R.; Blendy, J.A. A1D Adrenoceptor Signaling Is Required for Stimulus Induced Locomotor Activity. Mol. Psychiatry 2003, 8, 664–672. [Google Scholar] [CrossRef] [Green Version]
- Buckner, S.A.; Milicic, I.; Daza, A.; Lynch, J.J.; Kolasa, T.; Nakane, M.; Sullivan, J.P.; Brioni, J.D. A-315456: A selective α1D-adrenoceptor antagonist with minimal dopamine D2 and 5-HT1A receptor affinity. Eur. J. Pharmacol. 2001, 433, 123–127. [Google Scholar] [CrossRef]
- Saunders, C.; Limbird, L.E. Localization and trafficking of α2-adrenergic receptor subtypes in cells and tissues. Pharmacol. Ther. 1999, 84, 193–205. [Google Scholar] [CrossRef]
- Sastre, M.; García-Sevilla, J.A. α 2-Adrenoceptor Subtypes Identified by [3H]RX821002 Binding in the Human Brain: The Agonist Guanoxabenz Does Not Discriminate Different Forms of the Predominant α2A Subtype. J. Neurochem. 1994, 63, 1077–1085. [Google Scholar] [CrossRef] [PubMed]
- Gilsbach, R.; Hein, L. Are the pharmacology and physiology of α 2adrenoceptors determined by α 2-heteroreceptors and autoreceptors respectively? Br. J. Pharmacol. 2012, 165, 90–102. [Google Scholar] [CrossRef] [PubMed]
- Wasilewska, A.; Sączewski, F.; Hudson, A.L.; Ferdousi, M.; Scheinin, M.; Laurila, J.M.; Rybczyńska, A.; Boblewski, K.; Lehmann, A. Fluorinated analogues of marsanidine, a highly α2-AR/imidazoline I1 binding site-selective hypotensive agent. Synthesis and biological activities. Eur. J. Med. Chem. 2014, 87, 386–397. [Google Scholar] [CrossRef] [PubMed]
- Krzyczmonik, A.; Keller, T.; López-Picón, F.R.; Forsback, S.; Kirjavainen, A.K.; Takkinen, J.S.; Wasilewska, A.; Scheinin, M.; Haaparanta-Solin, M.; Sączewski, F.; et al. Radiosynthesis and Preclinical Evaluation of an α2A-Adrenoceptor Tracer Candidate, 6-[18F]Fluoro-marsanidine. Mol. Imaging Biol. 2019, 21, 879–887. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Prabhakaran, J.; Majo, V.J.; Milak, M.S.; Mali, P.; Savenkova, L.; Mann, J.J.; Parsey, R.V.; Kumar, J.S.D. Synthesis and in vivo evaluation of [11C]MPTQ: A potential PET tracer for alpha2A-adrenergic receptors. Bioorg. Med. Chem. Lett. 2010, 20, 3654–3657. [Google Scholar] [CrossRef]
- Arponen, E.; Helin, S.; Marjamäki, P.; Grönroos, T.; Holm, P.; Löyttyniemi, E.; Någren, K.; Scheinin, M.; Haaparanta-Solin, M.; Sallinen, J.; et al. A PET tracer for brain α2C adrenoceptors, 11C-ORM-13070: Radiosynthesis and preclinical evaluation in rats and knockout mice. J. Nucl. Med. 2014, 55, 1171–1177. [Google Scholar] [CrossRef] [Green Version]
- Kawamura, K.; Akiyama, M.; Yui, J.; Yamasaki, T.; Hatori, A.; Kumata, K.; Wakizaka, H.; Takei, M.; Nengaki, N.; Yanamoto, K.; et al. In vivo evaluation of limiting brain penetration of probes for α2C-adrenoceptor using small-animal positron emission tomography. ACS Chem. Neurosci. 2010, 1, 520–528. [Google Scholar] [CrossRef] [Green Version]
- Sallinen, J.; Höglund, I.; Engström, M.; Lehtimäki, J.; Virtanen, R.; Sirviö, J.; Wurster, S.; Savola, J.M.; Haapalinna, A. Pharmacological characterization and CNS effects of a novel highly selective α2C-adrenoceptor antagonist JP-1302. Br. J. Pharmacol. 2007, 150, 391–402. [Google Scholar] [CrossRef] [Green Version]
- Luoto, P.; Suilamo, S.; Oikonen, V.; Arponen, E.; Helin, S.; Herttuainen, J.; Hietamäki, J.; Holopainen, A.; Kailajärvi, M.; Peltonen, J.M.; et al. 11C-ORM-13070, a novel PET ligand for brain α2C-adrenoceptors: Radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men. Eur. J. Nucl. Med. Mol. Imaging 2014, 41, 1947–1956. [Google Scholar] [CrossRef]
- Sscarpace, P.J.; Abrass, I.B. Alpha- and beta-adrenergic receptor function in the brain during senescence. Neurobiol. Aging 1988, 9, 53–58. [Google Scholar] [CrossRef]
- Pandey, S.C.; Ren, X.; Sagen, J.; Pandey, G.N. β-Adrenergic receptor subtypes in stress-induced behavioral depression. Pharmacol. Biochem. Behav. 1995, 51, 339–344. [Google Scholar] [CrossRef]
- Wallukat, G. The β-adrenergic receptors. Herz 2002, 27, 683–690. [Google Scholar] [CrossRef] [PubMed]
- Lu’O’Ng, K.V.Q.; Nguyen, L.T.H. The role of beta-adrenergic receptor blockers in Alzheimer’s disease: Potential genetic and cellular signaling mechanisms. Am. J. Alzheimers. Dis. Demen. 2013, 28, 427–439. [Google Scholar] [CrossRef] [PubMed]
- O’Dell, T.J.; Connor, S.A.; Guglietta, R.; Nguyen, P.V. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus. Learn. Mem. 2015, 22, 461–471. [Google Scholar] [CrossRef] [Green Version]
- Gelinas, J.; Nguyen, P. Neuromodulation of Hippocampal Synaptic Plasticity, Learning, and Memory by Noradrenaline. Cent. Nerv. Syst. Agents Med. Chem. 2008, 7, 17–33. [Google Scholar] [CrossRef]
- Wachter, S.B.; Gilbert, E.M. Beta-adrenergic receptors, from their discovery and characterization through their manipulation to beneficial clinical application. Cardiology 2012, 122, 104–112. [Google Scholar] [CrossRef]
- Joyce, J.N.; Lexow, N.; Kim, S.J.; Artymyshyn, R.; Senzon, S.; Lawerence, D.; Cassanova, M.F.; Kleinman, J.E.; Bird, E.D.; Winokur, A. Distribution of beta-adrenergic receptor subtypes in human post-mortem brain: Alterations in limbic regions of schizophrenics. Synapse 1992, 10, 228–246. [Google Scholar] [CrossRef]
- Waarde, A.; Vaalburg, W.; Doze, P.; Bosker, F.; Elsinga, P. PET Imaging of Beta-Adrenoceptors in Human Brain: A Realistic Goal or a Mirage? Curr. Pharm. Des. 2005, 10, 1519–1536. [Google Scholar] [CrossRef] [Green Version]
- Pike, V.W.; Law, M.P.; Osman, S.; Davenport, R.J.; Rimoldi, O.; Giardinà, D.; Camici, P.G. Selection, design and evaluation of new radioligands for PET studies of cardiac adrenoceptors. Pharm. Acta Helv. 2000, 74, 191–200. [Google Scholar] [CrossRef]
- Chen, X.; Werner, R.A.; Javadi, M.S.; Maya, Y.; Decker, M.; Lapa, C.; Herrmann, K.; Higuchi, T. Radionuclide imaging of neurohormonal system of the heart. Theranostics 2015, 5, 545–558. [Google Scholar] [CrossRef]
- Logan, J.; Wang, G.J.; Telang, F.; Fowler, J.S.; Alexoff, D.; Zabroski, J.; Jayne, M.; Hubbard, B.; King, P.; Carter, P.; et al. Imaging the norepinephrine transporter in humans with (S,S)-[11C]O-methyl reboxetine and PET: Problems and progress. Nucl. Med. Biol. 2007, 34, 667–679. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Kudo, T.; Lapa, C.; Buck, A.; Higuchi, T. Recent advances in radiotracers targeting norepinephrine transporter: Structural development and radiolabeling improvements. J. Neural Transm. 2020, 127, 851–873. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zeng, F.; Mun, J.; Jarkas, N.; Stehouwer, J.S.; Voll, R.J.; Tamagnan, G.D.; Howell, L.; Votaw, J.R.; Kilts, C.D.; Nemeroff, C.B.; et al. Synthesis, Radiosynthesis, and Biological Evaluation of Carbon-11 and Fluorine-18 Labeled Reboxetine Analogs: Potential Positron Emission Tomography Radioligands for in Vivo Imaging of the Norepinephrine Transporter. J. Med. Chem. 2009, 52, 62–73. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moriguchi, S.; Kimura, Y.; Ichise, M.; Arakawa, R.; Takano, H.; Seki, C.; Ikoma, Y.; Takahata, K.; Nagashima, T.; Yamada, M.; et al. PET quantification of the norepinephrine transporter in human brain with (S,S)-18F-FMeNER-D2. J. Nucl. Med. 2017, 58, 1140–1145. [Google Scholar] [CrossRef] [Green Version]
- Narayanaswami, V.; Drake, L.R.; Brooks, A.F.; Meyer, J.H.; Houle, S.; Kilbourn, M.R.; Scott, P.J.H.; Vasdev, N. Classics in Neuroimaging: Development of PET Tracers for Imaging Monoamine Oxidases. ACS Chem. Neurosci. 2019, 10, 1867–1871. [Google Scholar] [CrossRef] [Green Version]
- Fowler, J.S.; Logan, J.; Shumay, E.; Alia-Klein, N.; Wang, G.J.; Volkow, N.D. Monoamine oxidase: Radiotracer chemistry and human studies. J. Label. Compd. Radiopharm. 2015, 58, 51–64. [Google Scholar] [CrossRef]
- Narayanaswami, V.; Dahl, K.; Bernard-Gauthier, V.; Josephson, L.; Cumming, P.; Vasdev, N. Emerging PET Radiotracers and Targets for Imaging of Neuroinflammation in Neurodegenerative Diseases: Outlook Beyond TSPO. Mol. Imaging 2018, 17, 1–25. [Google Scholar] [CrossRef] [Green Version]
- Piascik, M.T.; Perez, D.M. α1-Adrenergic receptors: New insights and directions. J. Pharmacol. Exp. Ther. 2001, 298, 403–410. [Google Scholar]
- Graham, R.M.; Perez, D.M.; Hwa, J.; Piascik, M.T. α1 -Adrenergic Receptor Subtypes. Circ. Res. 1996, 78, 737–749. [Google Scholar] [CrossRef]
- Chen, Z.J.; Minneman, K.P. Recent progress in α1-adrenergic receptor research. Acta Pharmacol. Sin. 2005, 26, 1281–1287. [Google Scholar] [CrossRef]
- O’Connell, T.D.; Jensen, B.C.; Baker, A.J.; Simpson, P.C. Cardiac alpha1-adrenergic receptors: Novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacol. Rev. 2014, 66, 308–333. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jensen, B.C.; O’Connell, T.D.; Simpson, P.C. Alpha-1-adrenergic receptors in heart failure: The adaptive arm of the cardiac response to chronic catecholamine stimulation. J. Cardiovasc. Pharmacol. 2014, 63, 291–301. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morrow, A.L.; Creese, I. Characterization of Alpha-1-Adrenergic Receptor Subtypes in Rat-Brain—A Reevaluation of [H-3] Wb4104 and [H-3] Prazosin Binding. Mol. Pharmacol. 1986, 29, 321–330. [Google Scholar] [PubMed]
- Romero-grimaldi, C.; Moreno-lo, B. Age-Dependent Effect of Nitric Oxide on Subventricular Zone and Olfactory Bulb. J. Comp. Neurol. 2008, 346, 339–346. [Google Scholar] [CrossRef] [PubMed]
- Campeau, S.; Nyhuis, T.J.; Kryskow, E.M.; Masini, C.V.; Babb, J.A.; Sasse, S.K.; Greenwood, B.N.; Fleshner, M.; Day, H.E.W. Stress rapidly increases alpha 1d adrenergic receptor mRNA in the rat dentate gyrus. Brain Res. 2010, 1323, 109–118. [Google Scholar] [CrossRef] [Green Version]
- Szot, P.; White, S.S.; Greenup, J.L.; Leverenz, J.B.; Peskind, E.R.; Raskind, M.A. Changes in Adrenoreceptors in The Prefrontal Cortex Of Subjects With Dementia: Evidence Of Compensatory Changes. Neuroscience 2007, 146, 471–480. [Google Scholar] [CrossRef] [Green Version]
- Perez, D.M.; Doze, V.A. Cardiac and neuroprotection regulated by alpha1-AR subtypes. J. Recept Signal. Transduct Res. 2011, 31, 98–110. [Google Scholar] [CrossRef] [Green Version]
- Sica, D. Alpha-1 adrenergic Blockers: Current Usage Considerations. J. Clin. Hypertens. 2005, 7, 757–762. [Google Scholar] [CrossRef]
- Miriam, H.; Hein, L. α1-Adrenozeptor-Antagonisten. Bei BPS und Hypertonie. Pharm. unserer Zeit 2008, 37, 290–295. [Google Scholar] [CrossRef]
- Law, M.P.; Osman, S.; Pike, V.W.; Davenport, R.J.; Cunningham, V.J.; Rimoldi, O.; Rhodes, C.G.; Giardinà, D.; Camici, P.G. Evaluation of [11C]GB67, a novel radioligand for imaging myocardial (α1-adrenoceptors with positron emission tomography. Eur. J. Nucl. Med. 2000, 27, 7–17. [Google Scholar] [CrossRef]
- Nyberg, S.; Eriksson, B.; Oxenstierna, G.; Halldin, C.; Farde, L. Suggested minimal effective dose of risperidone based on PET-measured D2 and 5-HT(2A) receptor occupancy in schizophrenic patients. Am. J. Psychiatry 1999, 156, 869–875. [Google Scholar] [CrossRef] [PubMed]
- Nyberg, S.; Olsson, H.; Nilsson, U.; Maehlum, E.; Halldin, C.; Farde, L. Low striatal and extra-striatal D2 receptor occupancy during treatment with the atypical antipsychotic sertindole. Psychopharmacology (Berl.) 2002, 162, 37–41. [Google Scholar] [CrossRef]
- Balle, T.; Perregaard, J.; Ramirez, M.T.; Larsen, A.K.; Søby, K.K.; Liljefors, T.; Andersen, K. Synthesis and structure-affinity relationship investigations of 5-heteroaryl-substituted analogues of the antipsychotic sertindole. A new class of highly selective α1 adrenoceptor antagonists. J. Med. Chem. 2003, 46, 265–283. [Google Scholar] [CrossRef] [PubMed]
- Balle, T.; Halldin, C.; Andersen, L.; Alifrangis, L.H.; Badolo, L.; Jensen, K.G.; Chou, Y.W.; Andersen, K.; Perregaard, J.; Farde, L. New α1-adrenoceptor antagonists derived from the antipsychotic sertindole—Carbon-11 labelling and pet examination of brain uptake in the cynomolgus monkey. Nucl. Med. Biol. 2004, 31, 327–336. [Google Scholar] [CrossRef] [PubMed]
- Airaksinen, A.J.; Finnema, S.J.; Balle, T.; Varnäs, K.; Bang-Andersen, B.; Gulyás, B.; Farde, L.; Halldin, C. Radiosynthesis and evaluation of new α1-adrenoceptor antagonists as PET radioligands for brain imaging. Nucl. Med. Biol. 2013, 40, 747–754. [Google Scholar] [CrossRef]
- Risgaard, R.; Ettrup, A.; Balle, T.; Dyssegaard, A.; Hansen, H.D.; Lehel, S.; Madsen, J.; Pedersen, H.; Püschl, A.; Badolo, L.; et al. Radiolabelling and PET brain imaging of the α1-adrenoceptor antagonist Lu AE43936. Nucl. Med. Biol. 2013, 40, 135–140. [Google Scholar] [CrossRef]
- Jorgensen, M.; Jorgensen, P.N.; Christoffersen, C.T.; Jensen, K.G.; Balle, T.; Bang-Andersen, B. Discovery of novel α1-adrenoceptor ligands based on the antipsychotic sertindole suitable for labeling as PET ligands. Bioorg. Med. Chem. 2013, 21, 196–204. [Google Scholar] [CrossRef]
- Bøgesø, K.P.; Arnt, J.; Hyttel, J.; Pedersen, H.; Liljefors, T. Octoclothepin Enantiomers. A Reinvestigation of Their Biochemical and Pharmacological Activity in Relation to a New Receptor-Interaction Model for Dopamine D-2 Receptor Antagonists. J. Med. Chem. 1991, 34, 2023–2030. [Google Scholar] [CrossRef]
- Liow, J.S.; Lu, S.; McCarron, J.A.; Hong, J.; Musachio, J.L.; Pike, V.W.; Innis, R.B.; Zoghbi, S.S. Effect of a P-Glycoprotein Inhibitor, Cyclosporin A, on the Disposition in Rodent Brain and Blood of the 5-HT1A Receptor Radioligand, [11C](R)-(––)-RWAY. Synapse 2007, 61, 96–105. [Google Scholar] [CrossRef]
- Roberts, L.R.; Bryans, J.; Conlon, K.; McMurray, G.; Stobie, A.; Whitlock, G.A. Novel 2-imidazoles as potent, selective and CNS penetrant α1A adrenoceptor partial agonists. Bioorg. Med. Chem. Lett. 2008, 18, 6437–6440. [Google Scholar] [CrossRef]
- Whitlock, G.A.; Brennan, P.E.; Roberts, L.R.; Stobie, A. Potent and selective α1A adrenoceptor partial agonists-Novel imidazole frameworks. Bioorg. Med. Chem. Lett. 2009, 19, 3118–3121. [Google Scholar] [CrossRef] [PubMed]
- Bücheler, M.M.; Hadamek, K.; Hein, L. Two α2-adrenergic receptor subtypes, α2A and α2C, inhibit transmitter release in the brain of gene-targeted mice. Neuroscience 2002, 109, 819–826. [Google Scholar] [CrossRef]
- Nguyen, V.; Tiemann, D.; Park, E.; Salehi, A. Alpha-2 Agonists. Anesthesiol. Clin. 2017, 35, 233–245. [Google Scholar] [CrossRef] [PubMed]
- Khan, Z.P.; Ferguson, C.N.; Jones, R.M. Alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 1999, 54, 146–165. [Google Scholar] [CrossRef]
- Paciorek, P.M.; Pierce, V.; Shepperson, N.B.; Waterfall, J.F. An investigation into the selectivity of a novel series of benzoquinolizines for α2-adrenoceptors in vivo. Br. J. Pharmacol. 1984, 82, 127–134. [Google Scholar] [CrossRef]
- Pettibone, D.J.; Flagg, S.D.; Totarol, J.A.; Clineschmidt, B.V.; Huff, J.R.; Young, S.D.; Chen, R. [3H]L-657, 743 (MK-912): A new, high affinity, selective radioligand for brain α-2 adrenoceptors. Life Sci. 1989, 44, 459–467. [Google Scholar] [CrossRef]
- Pleus, R.C.; Shiue, C.Y.; Shiue, G.G.; Rysavy, J.A.; Huang, H.; Cornish, K.G.; Sunderland, J.J.; Bylund, D.B. Synthesis and biodistribution of the alpha 2-adrenergic receptor antagonist (11C)WY26703. Use as a radioligand for positron emission tomography. Receptor 1992, 2, 241–252. [Google Scholar]
- Shiue, C.Y.; Pleus, R.C.; Shiue, G.G.; Rysavy, J.A.; Sunderland, J.J.; Cornish, K.G.; Young, S.D.; Bylund, D.B. Synthesis and biological evaluation of [11C]MK-912 as an α2- adrenergic receptor radioligand for PET studies. Nucl. Med. Biol. 1998, 25, 127–133. [Google Scholar] [CrossRef]
- BK, F.D.; Terrazzino, S.; Tavitian, B.; Hinnen, F.; Vaufrey, F.; Crouzel, C. XIIth international symposium on radiopharmaceutical chemistry: Abstracts and programme. J. Label. Compd. Radiopharm. 1997, 40, 1–72. [Google Scholar] [CrossRef]
- Hume, S.P.; Hirani, E.; Opacka-Juffry, J.; Osman, S.; Myers, R.; Gunn, R.N.; McCarron, J.A.; Clark, R.D.; Melichar, J.; Nutt, D.J.; et al. Evaluation of [O-methyl-11C]RS.15385-197 as a positron emission tomography radioligand for central α2-adrenoceptors. Eur. J. Nucl. Med. 2000, 27, 475–484. [Google Scholar] [CrossRef]
- Roeda, D.; Sipil, H.T.; Bramoull, Y.; Enas, J.D.; Vaufrey, F.; Doll, F.; Crouzel, C. Synthesis of [11C]atipamezole, a potential PET ligand for the α2-adrenergic receptor in the brain. J. Label. Compd. Radiopharm. 2002, 45, 37–47. [Google Scholar] [CrossRef]
- Marthi, K.; Bender, D.; Watanabe, H.; Smith, D.F. PET evaluation of a tetracyclic, atypical antidepressant, [N-methyl-11C]mianserin, in the living porcine brain. Nucl. Med. Biol. 2002, 29, 317–319. [Google Scholar] [CrossRef]
- Marthi, K.; Bender, D.; Gjedde, A.; Smith, D.F. [11C]Mirtazapine for PET neuroimaging: Radiosynthesis and initial evaluation in the living porcine brain. Eur. Neuropsychopharmacol. 2002, 12, 427–432. [Google Scholar] [CrossRef]
- Marthi, K.; Jakobsen, S.; Bender, D.; Hansen, S.B.; Smith, S.B.; Hermansen, F.; Rosenberg, R.; Smith, D.F. [N-methyl-11C]Mirtazapine for positron emission tomography neuroimaging of antidepressant actions in humans. Psychopharmacology (Berl.) 2004, 174, 260–265. [Google Scholar] [CrossRef] [PubMed]
- Smith, D.F.; Stork, B.S.; Wegener, G.; Ashkanian, M.; Jakobsen, S.; Bender, D.; Audrain, H.; Vase, K.H.; Hansen, S.B.; Videbech, P.; et al. [11C]mirtazapine binding in depressed antidepressant nonresponders studied by PET neuroimaging. Psychopharmacology (Berl.) 2009, 206, 133–140. [Google Scholar] [CrossRef] [PubMed]
- Van der Mey, M.; Windhorst, A.D.; Klok, R.P.; Herscheid, J.D.M.; Kennis, L.E.; Bischoff, F.; Bakker, M.; Langlois, X.; Heylen, L.; Jurzak, M.; et al. Synthesis and biodistribution of [11C]R107474, a new radiolabeled α2-adrenoceptor antagonist. Bioorg. Med. Chem. 2006, 14, 4526–4534. [Google Scholar] [CrossRef]
- Jakobsen, S.; Pedersen, K.; Smith, D.F.; Jensen, S.B.; Munk, O.L.; Cumming, P. Detection of a 2 -Adrenergic Receptors in Brain of Living Pig with 11 C-Yohimbine. J. Nucl. Med. 2006, 47, 2008–2015. [Google Scholar]
- Nahimi, A.; Jakobsen, S.; Munk, O.L.; Vang, K.; Phan, J.A.; Rodell, A.; Gjedde, A. Mapping α2 adrenoceptors of the human brain with11C-yohimbine. J. Nucl. Med. 2015, 56, 392–398. [Google Scholar] [CrossRef] [Green Version]
- Andrés, J.I.; Alcázar, J.; Alonso, J.M.; Alvarez, R.M.; Bakker, M.H.; Biesmans, I.; Cid, J.M.; De Lucas, A.I.; Fernández, J.; Font, L.M.; et al. Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with α2- adrenoceptor blocking activity. J. Med. Chem. 2005, 48, 2054–2071. [Google Scholar] [CrossRef]
- Sa̧czewski, F.; Kornicka, A.; Rybczyńska, A.; Hudson, A.L.; Shu, S.M.; Gdaniec, M.; Boblewski, K.; Lehmann, A. 1-[(imidazolidin-2-yl)imino]indazole. Highly α2/I 1 selective agonist: Synthesis, X-ray structure, and biological activity. J. Med. Chem. 2008, 51, 3599–3608. [Google Scholar] [CrossRef]
- Hagihara, K.; Kashima, H.; Iida, K.; Enokizono, J.; Uchida, S.I.; Nonaka, H.; Kurokawa, M.; Shimada, J. Novel 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran derivatives as selective α2C-adrenergic receptor antagonists. Bioorg. Med. Chem. Lett. 2007, 17, 1616–1621. [Google Scholar] [CrossRef] [PubMed]
- Finnema, S.J.; Hughes, Z.A.; Haaparanta-Solin, M.; Stepanov, V.; Nakao, R.; Varnäs, K.; Varrone, A.; Arponen, E.; Marjamäki, P.; Pohjanoksa, K.; et al. Amphetamine decreases α2C-adrenoceptor binding of [11C]ORM-13070: A PET study in the primate brain. Int. J. Neuropsychopharmacol. 2015, 18, 1–10. [Google Scholar] [CrossRef] [PubMed]
- Palacios, J.M.; Kuhar, M.J. Beta adrenergic receptor localization in rat brain by light microscopic autoradiography. Neurochem. Int. 1982, 4, 473–490. [Google Scholar] [CrossRef]
- Cash, R.; Ruberg, M.; Raisman, R.; Agid, Y. Adrenergic receptors in Parkinson’s disease. Brain Res. 1984, 322, 269–275. [Google Scholar] [CrossRef]
- Hopfner, F.; Höglinger, G.U.; Kuhlenbäumer, G.; Pottegård, A.; Wod, M.; Christensen, K.; Tanner, C.M.; Deuschl, G. β-adrenoreceptors and the risk of Parkinson’s disease. Lancet Neurol. 2020, 19, 247–254. [Google Scholar] [CrossRef]
- Klimek, V.; Rajkowska, G.; Luker, S.N.; Dilley, G.; Meltzer, H.Y.; Overholser, J.C.; Stockmeier, C.A.; Ordway, G.A. Brain noradrenergic receptors in major depression and schizophrenia. Neuropsychopharmacology 1999, 21, 69–81. [Google Scholar] [CrossRef]
- Ueki, J.; Rhodes, C.G.; Hughes, J.M.; De Silva, R.; Lefroy, D.C.; Ind, P.W.; Qing, F.; Brady, F.; Luthra, S.K.; Steel, C.J. In vivo quantification of pulmonary B-adrenoceptor density in humans with (S)-[11C]CGP-12177 and PET. Am. Physiol. Soc. 1993, 75, 559–565. [Google Scholar] [CrossRef] [PubMed]
- Elsinga, P.H.; Doze, P.; Van Waarde, A.; Pieterman, R.M.; Blanksma, P.K.; Willemsen, A.T.M.; Vaalburg, W. Imaging of β-adrenoceptors in the human thorax using (S)-[11C]CGP12388 and positron emission tomography. Eur. J. Pharmacol. 2001, 433, 173–176. [Google Scholar] [CrossRef]
- Berger, G.; Maziere, M.; Prenant, C.; Sastre, J.; Syrota, A.; Comar, D. Synthesis of 11 C propranolol. J. Radioanal. Chem. 1982, 74, 301–306. [Google Scholar] [CrossRef]
- Antoni, G.; Ulin, J.; Långström, B. Synthesis of the 11C-labelled β-adrenergic receptor ligands atenolol, metoprolol and propranolol. Int. J. Radiat. Appl. Instrum. Part A 1989, 40, 561–564. [Google Scholar] [CrossRef]
- Berridge, M.S.; Nelson, A.D.; Zheng, L.; Leisure, G.P.; Miraldi, F. Specific beta-adrenergic receptor binding of carazolol measured with PET. J. Nucl. Med. 1994, 35, 1665–1676. [Google Scholar]
- Zheng, L.; Berridge, M.S.; Ernsberger, P. Synthesis, Binding Properties, and 18F Labeling of Fluorocarazolol, a High-Affinity β-Adrenergic Receptor Antagonist. J. Med. Chem. 1994, 37, 3219–3230. [Google Scholar] [CrossRef] [PubMed]
- Doze, P.; Van Waarde, A.; Elsinga, P.H.; Van-Loenen Weemaes, A.M.A.; Willemsen, A.T.M.; Vaalburg, W. Validation of S-1′-[18F]fluorocarazolol for in vivo imaging and quantification of cerebral β-adrenoceptors. Eur. J. Pharmacol. 1998, 353, 215–226. [Google Scholar] [CrossRef]
- Doze, P.; Elsinga, P.H.; De Vries, E.F.J.; Van Waarde, A.; Vaalburg, W. Mutagenic activity of a fluorinated analog of the beta-adrenoceptor ligand carazolol in the Ames test. Nucl. Med. Biol. 2000, 27, 315–319. [Google Scholar] [CrossRef]
- Tewson, T.J.; Stekhova, S.; Kinsey, B.; Chen, L.; Wiens, L.; Barber, R. Synthesis and biodistribution of R- and S-isomers of [18F]- fluoropropranolol, a lipophilic ligand for the β-adrenergic receptor. Nucl. Med. Biol. 1999, 26, 891–896. [Google Scholar] [CrossRef]
- Moresco, R.M.; Matarrese, M.; Soloviev, D.; Simonelli, P.; Rigamonti, M.; Gobbo, C.; Todde, S.; Carpinelli, A.; Galli Kienle, M.; Fazio, F. Synthesis and in vivo evaluation of [11C]ICI 118551 as a putative subtype selective β2-adrenergic radioligand. Int. J. Pharm. 2000, 204, 101–109. [Google Scholar] [CrossRef]
- Soloviev, D.V.; Matarrese, M.; Moresco, R.M.; Todde, S.; Bonasera, T.A.; Sudati, F.; Simonelli, P.; Magni, F.; Colombo, D.; Carpinelli, A.; et al. Asymmetric synthesis and preliminary evaluation of (R)- and (S)-[11C]bisoprolol, a putative β1-selective adrenoceptor radioligand. Neurochem. Int. 2001, 38, 169–180. [Google Scholar] [CrossRef]
- Doze, P.; Elsinga, P.H.; Maas, B.; Van Waarde, A.; Wegman, T.; Vaalburg, W. Synthesis and evaluation of radiolabeled antagonists for imaging of β-adrenoceptors in the brain with PET. Neurochem. Int. 2002, 40, 145–155. [Google Scholar] [CrossRef]
- Doze, P.; Van Waarde, A.; Tewson, T.J.; Vaalburg, W.; Elsinga, P.H. Synthesis and evaluation of (S)-[18F]-fluoroethylcarazolol for in vivo β-adrenoceptor imaging in the brain. Neurochem. Int. 2002, 41, 17–27. [Google Scholar] [CrossRef]
- van Waarde, A.; Doorduin, J.; de Jong, J.R.; Dierckx, R.A.; Elsinga, P.H. Synthesis and preliminary evaluation of (S)-[11C]-exaprolol, a novel β-adrenoceptor ligand for PET. Neurochem. Int. 2008, 52, 729–733. [Google Scholar] [CrossRef]
- Stephenson, K.A.; van Oosten, E.M.; Wilson, A.A.; Meyer, J.H.; Houle, S.; Vasdev, N. Synthesis and preliminary evaluation of [18F]-fluoro-(2S)-Exaprolol for imaging cerebral β-adrenergic receptors with PET. Neurochem. Int. 2008, 53, 173–179. [Google Scholar] [CrossRef] [PubMed]
- Mirfeizi, L.; Rybczynska, A.A.; van Waarde, A.; Campbell-Verduyn, L.; Feringa, B.L.; Dierckx, R.A.J.O.; Elsinga, P.H. [18F]-(fluoromethoxy)ethoxy)methyl)-1H-1,2,3-triazol-1-yl)propan-2-ol ([18F FPTC) a novel PET-ligand for cerebral beta-adrenoceptors. Nucl. Med. Biol. 2014, 41, 203–209. [Google Scholar] [CrossRef] [PubMed]
Compound | Receptor Ki (nM) | ||||
---|---|---|---|---|---|
α1A | α1B | α1D | D2 | 5HT2C | |
1 | 0.37 | 0.33 | 0.66 | 0.45 | 0.55 |
2 | 0.23 | 1.1 | 2.0 | 140 | 330 |
3 | 3.0 | 6.0 | 8.6 | 310 | 1500 |
4 | 0.16 | 6.4 | 15 | 220 | - |
5 | 0.52 | 1.9 | 2.5 | 120 | - |
6 | 0.37 | 0.33 | 0.66 | 0.45 | 0.51 |
(R)-7 | 0.43 | 0.27 | 0.64 | 31 | 8.0 |
(S)-7 | 0.16 | 0.20 | 0.21 | 4.5 | 93 |
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Alluri, S.R.; Kim, S.W.; Volkow, N.D.; Kil, K.-E. PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives. Molecules 2020, 25, 4017. https://doi.org/10.3390/molecules25174017
Alluri SR, Kim SW, Volkow ND, Kil K-E. PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives. Molecules. 2020; 25(17):4017. https://doi.org/10.3390/molecules25174017
Chicago/Turabian StyleAlluri, Santosh Reddy, Sung Won Kim, Nora D. Volkow, and Kun-Eek Kil. 2020. "PET Radiotracers for CNS-Adrenergic Receptors: Developments and Perspectives" Molecules 25, no. 17: 4017. https://doi.org/10.3390/molecules25174017