Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012
Abstract
:1. Introduction
2. PDE2 Radioligands
3. PDE4 Radioligands
4. PDE5 Radioligands
5. PDE7 Radioligands
6. PDE10 Radioligands
6.1. Radioligands Structurally Related to the PDE10A Inhibitor MP-10
6.2. Radioligands Structurally not Derived from the PDE10A Inhibitor MP-10
7. Summary and Concluding Remarks
Acknowledgments
Conflicts of Interest
References
- Wahl, R.L.; Wagner, H.N. Principles and Practice of PET and PET/CT, 2nd ed.; Wolters Kluwer/Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2009; p. 729. [Google Scholar]
- Brust, P.; van den Hoff, J.; Steinbach, J. Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography. Neurosci. Bull. 2014, 30, 777–811. [Google Scholar] [CrossRef] [PubMed]
- Gallamini, A.; Zwarthoed, C.; Borra, A. Positron emission tomography (PET) in oncology. Cancers 2014, 6, 1821–1889. [Google Scholar] [CrossRef] [PubMed]
- Tee, S.S.; Keshari, K.R. Novel approaches to imaging tumor metabolism. Cancer J. 2015, 21, 165–173. [Google Scholar] [CrossRef] [PubMed]
- Tarkin, J.M.; Joshi, F.R.; Rajani, N.K.; Rudd, J.H. PET imaging of atherosclerosis. Future Cardiol. 2015, 11, 115–131. [Google Scholar] [CrossRef] [PubMed]
- Jivraj, N.; Phinikaridou, A.; Shah, A.M.; Botnar, R.M. Molecular imaging of myocardial infarction. Basic Res. Cardiol. 2014, 109, 397. [Google Scholar] [CrossRef] [PubMed]
- Mier, W.; Mier, D. Advantages in functional imaging of the brain. Front. Hum. Neurosci. 2015, 9, 249. [Google Scholar] [CrossRef] [PubMed]
- Conti, M.; **, S.L. The molecular biology of cyclic nucleotide phosphodiesterases. Prog. Nucleic Acid Res. Mol. Biol. 1999, 63, 1–38. [Google Scholar] [PubMed]
- Bender, A.T.; Beavo, J.A. Cyclic nucleotide phosphodiesterases: Molecular regulation to clinical use. Pharmacol. Rev. 2006, 58, 488–520. [Google Scholar] [CrossRef] [PubMed]
- Omori, K.; Kotera, J. Overview of PDEs and their regulation. Circ. Res. 2007, 100, 309–327. [Google Scholar] [CrossRef] [PubMed]
- Hardman, J.G.; Robison, G.A.; Sutherland, E.W. Cyclic nucleotides. Annu. Rev. Physiol. 1971, 33, 311–336. [Google Scholar] [CrossRef] [PubMed]
- Francis, S.H.; Corbin, J.D. Cyclic nucleotide-dependent protein kinases: Intracellular receptors for cAMP and cGMP action. Crit. Rev. Clin. Lab. Sci. 1999, 36, 275–328. [Google Scholar] [CrossRef] [PubMed]
- Bos, J.L. Epac proteins: Multi-purpose cAMP targets. Trends Biochem. Sci. 2006, 31, 680–686. [Google Scholar] [CrossRef] [PubMed]
- Beavo, J.A.; Francis, S.H.; Houslay, M.D. Cyclic Nucleotide Phosphodiesterases in Health and Disease, 1st ed.; CRC Press: Boca Raton, FL, USA, 2006; p. 728. [Google Scholar]
- Francis, S.H.; Blount, M.A.; Corbin, J.D. Mammalian cyclic nucleotide phosphodiesterases: Molecular mechanisms and physiological functions. Physiol. Rev. 2011, 91, 651–690. [Google Scholar] [CrossRef] [PubMed]
- Weiss, B.; Hait, W.N. Selective cyclic nucleotide phosphodiesterase inhibitors as potential therapeutic agents. Annu. Rev. Pharmacol. Toxicol. 1977, 17, 441–477. [Google Scholar] [CrossRef] [PubMed]
- Weishaar, R.E.; Cain, M.H.; Bristol, J.A. A new generation of phosphodiesterase inhibitors: Multiple molecular forms of phosphodiesterase and the potential for drug selectivity. J. Med. Chem. 1985, 28, 537–545. [Google Scholar] [CrossRef] [PubMed]
- Schudt, C.; Winder, S.; Eltze, M.; Kilian, U.; Beume, R. Zardaverine: A cyclic AMP specific PDE III/IV inhibitor. Agents Actions Suppl. 1991, 34, 379–402. [Google Scholar] [PubMed]
- Lugnier, C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific therapeutic agents. Pharmacol. Ther. 2006, 109, 366–398. [Google Scholar] [CrossRef] [PubMed]
- Keravis, T.; Lugnier, C. Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: Benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Br. J. Pharmacol. 2012, 165, 1288–1305. [Google Scholar] [CrossRef] [PubMed]
- Fajardo, A.; Piazza, G.; Tinsley, H. The role of cyclic nucleotide signaling pathways in cancer: Targets for prevention and treatment. Cancers 2014, 6, 436–458. [Google Scholar] [CrossRef] [PubMed]
- Wang, Z.-Z.; Zhang, Y.; Zhang, H.-T.; Li, Y.-F. Phosphodiesterase: An interface connecting cognitive deficits to neuropsychiatric and neurodegenerative diseases. Curr. Pharm. Des. 2015, 21, 303–316. [Google Scholar] [CrossRef]
- DaSilva, J.N.; Valente, C.M.; Wilson, A.A.; Warsh, J.J.; Houle, S. Carbon-11 labeling of the selective inhibitors of phosphodiesterase IV RO20–1724 and rolipram. J. Label. Comp. Radiopharm. 1997, 40, 678–680. [Google Scholar]
- DaSilva, J.N.; Lourenco, C.M.; Meyer, J.H.; Hussey, D.; Potter, W.Z.; Houle, S. Imaging cAMP-specific phosphodiesterase-4 in human brain with R-[11C]rolipram and positron emission tomography. Eur. J. Nucl. Med. Mol. Imaging 2002, 29, 1680–1683. [Google Scholar] [CrossRef] [PubMed]
- Andrés, J.I.; De Angelis, M.; Alcazar, J.; Celen, S.; Bormans, G. Recent advances in positron emission tomography (PET) radiotracers for imaging phosphodiesterases. Curr. Top. Med. Chem. 2012, 12, 1224–1236. [Google Scholar] [CrossRef] [PubMed]
- Martins, T.J.; Mumby, M.C.; Beavo, J.A. Purification and characterization of a cyclic GMP-stimulated cyclic nucleotide phosphodiesterase from bovine tissues. J. Biol. Chem. 1982, 257, 1973–1979. [Google Scholar] [PubMed]
- Pyne, N.J.; Cooper, M.E.; Houslay, M.D. Identification and characterization of both the cytosolic and particulate forms of cyclic GMP-stimulated cyclic AMP phosphodiesterase from rat liver. Biochem. J. 1986, 234, 325–334. [Google Scholar] [CrossRef] [PubMed]
- Russwurm, C.; Zoidl, G.; Koesling, D.; Russwurm, M. Dual acylation of PDE2A splice variant 3: Targeting to synaptic membranes. J. Biol. Chem. 2009, 284, 25782–25790. [Google Scholar] [CrossRef] [PubMed]
- Martinez, S.E.; Wu, A.Y.; Glavas, N.A.; Tang, X.B.; Turley, S.; Hol, W.G.; Beavo, J.A. The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding. Proc. Natl. Acad. Sci. USA 2002, 99, 13260–13265. [Google Scholar] [CrossRef] [PubMed]
- Iffland, A.; Kohls, D.; Low, S.; Luan, J.; Zhang, Y.; Kothe, M.; Cao, Q.; Kamath, A.V.; Ding, Y.-H.; Ellenberger, T. Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system. Biochemistry 2005, 44, 8312–8325. [Google Scholar] [CrossRef] [PubMed]
- Pandit, J.; Forman, M.D.; Fennell, K.F.; Dillman, K.S.; Menniti, F.S. Mechanism for the allosteric regulation of phosphodiesterase 2A deduced from the X-ray structure of a near full-length construct. Proc. Natl. Acad. Sci. USA 2009, 106, 18225–18230. [Google Scholar] [CrossRef] [PubMed]
- DeNinno, M.P. Future directions in phosphodiesterase drug discovery. Bioorg. Med. Chem. Lett. 2012, 22, 6794–6800. [Google Scholar] [CrossRef] [PubMed]
- Kelly, M.P.; Adamowicz, W.; Bove, S.; Hartman, A.J.; Mariga, A.; Pathak, G.; Reinhart, V.; Romegialli, A.; Kleiman, R.J. Select 3′,5′-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain. Cell. Signal. 2014, 26, 383–397. [Google Scholar] [CrossRef] [PubMed]
- Lakics, V.; Karran, E.H.; Boess, F.G. Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Neuropharmacology 2010, 59, 367–374. [Google Scholar] [CrossRef] [PubMed]
- Menniti, F.S.; Faraci, W.S.; Schmidt, C.J. Phosphodiesterases in the CNS: Targets for drug development. Nat. Rev. Drug Discov. 2006, 5, 660–670. [Google Scholar] [CrossRef] [PubMed]
- Sadhu, K.; Hensley, K.; Florio, V.A.; Wolda, S.L. Differential expression of the cyclic GMP-stimulated phosphodiesterase PDE2A in human venous and capillary endothelial cells. J. Histochem. Cytochem. 1999, 47, 895–906. [Google Scholar] [CrossRef] [PubMed]
- Morita, H.; Murata, T.; Shimizu, K.; Okumura, K.; Inui, M.; Tagawa, T. Characterization of phosphodiesterase 2A in human malignant melanoma PMP cells. Oncol. Rep. 2013, 29, 1275–1284. [Google Scholar] [CrossRef] [PubMed]
- Drees, M.; Zimmermann, R.; Eisenbrand, G. 3′,5′-Cyclic nucleotide phosphodiesterase in tumor cells as potential target for tumor growth inhibition. Cancer Res. 1993, 53, 3058–3061. [Google Scholar] [PubMed]
- Durand, J.; Lampron, A.; Mazzuco, T.L.; Chapman, A.; Bourdeau, I. Characterization of differential gene expression in adrenocortical tumors harboring β-catenin (CTNNB1) mutations. J. Clin. Endocr. Metab. 2011, 96, E1206–E1211. [Google Scholar] [CrossRef] [PubMed]
- Dong, H.; Claffey, K.P.; Brocke, S.; Epstein, P.M. Inhibition of breast cancer cell migration by activation of cAMP signaling. Breast Cancer Res. Treat. 2015, 152, 17–28. [Google Scholar] [CrossRef] [PubMed]
- Stephenson, D.T.; Coskran, T.M.; Wilhelms, M.B.; Adamowicz, W.O.; O’Donnell, M.M.; Muravnick, K.B.; Menniti, F.S.; Kleiman, R.J.; Morton, D. Immunohistochemical localization of phosphodiesterase 2A in multiple mammalian species. J. Histochem. Cytochem. 2009, 57, 933–949. [Google Scholar] [CrossRef] [PubMed]
- Stephenson, D.T.; Coskran, T.M.; Kelly, M.P.; Kleiman, R.J.; Morton, D.; O’Neill, S.M.; Schmidt, C.J.; Weinberg, R.J.; Menniti, F.S. The distribution of phosphodiesterase 2A in the rat brain. Neuroscience 2012, 226, 145–155. [Google Scholar] [CrossRef] [PubMed]
- Stange, H.; Langen, B.; Egerland, U.; Hoefgen, N.; Priebs, M.; Malamas, M.S.; Erdel, J.J.; Ni, Y. Triazine Derivatives as Inhibitors of Phosphodiesterases. WO 2010/054253 A1, PCT/US2009/063633, 14 May 2010. [Google Scholar]
- Van Staveren, W.C.G.; Markerink-van Ittersum, M.; Steinbusch, H.W.M.; de Vente, J. The effects of phosphodiesterase inhibition on cyclic GMP and cyclic AMP accumulation in the hippocampus of the rat. Brain Res. 2001, 888, 275–286. [Google Scholar] [CrossRef]
- Suvarna, N.U.; O′Donnell, J.M. Hydrolysis of N-methyl-d-aspartate receptor-stimulated cAMP and cGMP by PDE4 and PDE2 phosphodiesterases in primary neuronal cultures of rat cerebral cortex and hippocampus. J. Pharmacol. Exp. Ther. 2002, 302, 249–256. [Google Scholar] [CrossRef] [PubMed]
- Blokland, A.; Schreiber, R.; Prickaerts, J. Improving memory: A role for phosphodiesterases. Curr. Pharm. Des. 2006, 12, 2511–2523. [Google Scholar] [CrossRef] [PubMed]
- Van Staveren, W.C.G.; Steinbusch, H.W.M.; Markerink-Van Ittersum, M.; Repaske, D.R.; Goy, M.F.; Kotera, J.; Omori, K.; Beavo, J.A.; de Vente, J. MRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain. J. Comp. Neurol. 2003, 467, 566–580. [Google Scholar] [CrossRef] [PubMed]
- Gomez, L.; Breitenbucher, J.G. PDE2 inhibition: Potential for the treatment of cognitive disorders. Bioorg. Med. Chem. Lett. 2013, 23, 6522–6527. [Google Scholar] [CrossRef] [PubMed]
- Zhang, C.; Yu, Y.; Ruan, L.; Wang, C.; Pan, J.; Klabnik, J.; Lueptow, L.; Zhang, H.-T.; O’Donnell, J.M.; Xu, Y. The roles of phosphodiesterase 2 in the central nervous and peripheral systems. Curr. Pharm. Des. 2015, 21, 274–290. [Google Scholar] [CrossRef]
- Masood, A.; Huang, Y.; Hajjhussein, H.; ** and mature rat brain. Neuroscience 1996, 72, 567–578. [Google Scholar] [CrossRef]
- Nieber, K.; Erdmann, S.; Briel, D.; Schwan, G.; Kubicova, L.; Barbar Asskar, G.; Sträter, N.; Zahn, M.; Brust, P.; Funke, U. Neue Halogenalkoxychinazoline, deren Herstellung und Verwendung. 00401P0051DE, 20 October 2010. [Google Scholar]
- Malamas, M.S.; Ni, Y.; Erdei, J.; Stange, H.; Schindler, R.; Lankau, H.-J.; Grunwald, C.; Fan, K.Y.; Parris, K.; Langen, B.; et al. Highly potent, selective, and orally active phosphodiesterase 10A inhibitors. J. Med. Chem. 2011, 54, 7621–7638. [Google Scholar] [CrossRef] [PubMed]
- Wagner, S.; Scheunemann, M.; Fischer, S.; Egerland, U.; Ludwig, F.-A.; Höfgen, N.; Steinbach, J.; Brust, P. 1-Arylimidazo[1,5a]quinoxalines as lead compounds for a PDE10A PET tracer. In Proceedings of Annual Congress of the European Association of Nuclear Medicine, Gothenburg, Sweden, 18–22 October 2014; OP163. p. S197.
- Wagner, S.; Scheunemann, M.; Dipper, K.; Egerland, U.; Hoefgen, N.; Steinbach, J.; Brust, P. Development of highly potent phosphodiesterase 10A (PDE10A) inhibitors: Synthesis and in vitro evaluation of 1,8-dipyridinyl- and 1-pyridinyl-substituted imidazo[1,5-a]quinoxalines. Eur. J. Med. Chem. 2016, 107, 97–108. [Google Scholar] [CrossRef] [PubMed]
- Wagner, S.; Kranz, M.; Hankir, M.; Deuther-Conrad, W.; Scheunemann, M.; Teodoro, R.; Wenzel, B.; Fischer, S.; Egerland, U.; Fenske, W.K.; et al. Evaluation of the new radioligand [18F]AQ-28A by small animal PET/MR demonstrates increse of PDE10A expression in striatum and brown adipose tissue (BAT) of obese mice. In Proceedings of the 21st International Symposium on Radiopharmaceutical Sciences, Columbia, MO, USA, 26–31 May 2015; 52. p. S52.
- Wagner, S.; Teodoro, R.; Deuther-Conrad, W.; Kranz, M.; Scheunemann, M.; Fischer, S.; Wenzel, B.; Egerland, U.; Hoefgen, N.; Steinbach, J.; et al. Radiosynthesis and biological evaluation of the new PDE10A radioligand [18F]AQ28A. J. Label. Comp. Radiopharm. 2015. submitted. [Google Scholar]
- Nawrocki, A.R.; Rodriguez, C.G.; Toolan, D.M.; Price, O.; Henry, M.; Forrest, G.; Szeto, D.; Keohane, C.A.; Pan, Y.; Smith, K.M.; et al. Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance. Diabetes 2014, 63, 300–311. [Google Scholar] [CrossRef] [PubMed]
- Barret, O.; Thomae, D.; Alagille, D.; Lee, H.; Papin, C.; Baldwin, R.; Jennings, D.; Marek, K.; Seibyl, J.; Tamagnan, G. First in vivo assessment of two PDE10 tracers [18F]MNI654 and [18F]MNI659. J. Nucl. Med. 2012, 53, 361. [Google Scholar]
- Barret, O.; Thomae, D.; Tavares, A.; Alagille, D.; Papin, C.; Waterhouse, R.; McCarthy, T.; Jennings, D.; Marek, K.; Russell, D.; et al. In vivo assessment and dosimetry of 2 novel PDE10A PET radiotracers in humans: 18F-MNI-659 and 18F-MNI-654. J. Nucl. Med. 2014, 55, 1297–1304. [Google Scholar] [CrossRef] [PubMed]
- Russell, D.S.; Barret, O.; Jennings, D.L.; Friedman, J.H.; Tamagnan, G.D.; Thomae, D.; Alagille, D.; Morley, T.J.; Papin, C.; Papapetropoulos, S.; et al. The phosphodiesterase 10 positron emission tomography tracer, [18F]MNI-659, as a novel biomarker for early huntington disease. J. Am. Med. Assoc. Neurol. 2014, 71, 1520–1528. [Google Scholar] [CrossRef] [PubMed]
- Russell, D.S.; Jennings, D.L.; Barret, O.; Tamagnan, G.D.; Carroll, V.M.; Caille, F.; Alagille, D.; Morley, T.J.; Papin, C.; Seibyl, J.P.; et al. Change in PDE10 across early Huntington disease assessed by [18F]MNI-659 and PET imaging. Neurology 2016, 86, 748–754. [Google Scholar] [CrossRef] [PubMed]
- Niccolini, F.; Haider, S.; Marques, T.R.; Muhlert, N.; Tziortzi, A.C.; Searle, G.E.; Natesan, S.; Piccini, P.; Kapur, S.; Rabiner, E.A.; et al. Altered PDE10A expression detectable early before symptomatic onset in Huntington’s disease. Brain 2015, 138, 3016–3029. [Google Scholar] [CrossRef] [PubMed]
- Niccolini, F.; Foltynie, T.; Marques, T.R.; Muhlert, N.; Tziortzi, A.C.; Searle, G.E.; Natesan, S.; Kapur, S.; Rabiner, E.A.; Gunn, R.N.; et al. Loss of phosphodiesterase 10A expression is associated with progression and severity in Parkinson’s disease. Brain 2015, 138, 3003–3015. [Google Scholar] [CrossRef] [PubMed]
- Marques, T.R.; Natesan, S.; Niccolini, F.; Politis, M.; Gunn, R.N.; Searle, G.E.; Howes, O.; Rabiner, E.A.; Kapur, S. Phosphodiesterase 10A in schizophrenia: A PET study using [11C]IMA107. Am. J. Psychiat. 2016. [Google Scholar] [CrossRef] [PubMed]
- Kehler, J.; Kilburn, J.P.; Estrada, S.; Christensen, S.R.; Wall, A.; Thibblin, A.; Lubberink, M.; Bundgaard, C.; Brennum, L.T.; Steiniger-Brach, B.; et al. Discovery and development of 11C-Lu AE92686 as a radioligand for PET imaging of phosphodiesterase 10A in the brain. J. Nucl. Med. 2014, 55, 1513–1518. [Google Scholar] [CrossRef] [PubMed]
- Bang-Andersen, B.; Kehler, J. Radiolabelled Phenylimidazole-Based Ligands. WO 2012/062319 A1, 18 May 2012. [Google Scholar]
- Ritzén, A.; Kehler, J.; Langgârd, M.; Nielsen, J.; Kilburn, J.P.; Farah, M.M. Novel Phenylimidazole Derivatives as PDE10A Enzyme Inhibitors. WO 2009/152825 A1, 23 December 2009. [Google Scholar]
- Hwang, D.-R.; Hu, E.; Rumfelt, S.; Easwaramoorthy, B.; Castrillon, J.; Davis, C.; Allen, J.R.; Chen, H.; Treanor, J.; Abi-Dargham, A.; et al. Initial characterization of a PDE10A selective positron emission tomography tracer [11C]AMG 7980 in non-human primates. Nucl. Med. Biol. 2014, 41, 343–349. [Google Scholar] [CrossRef] [PubMed]
- Hwang, D.-R.; Hu, E.; Allen, J.R.; Davis, C.; Treanor, J.; Miller, S.; Chen, H.; Shi, B.; Narayanan, T.K.; Barret, O.; et al. Radiosynthesis and initial characterization of a PDE10A specific PET tracer [18F]AMG 580 in non-human primates. Nucl. Med. Biol. 2015, 42, 654–663. [Google Scholar] [CrossRef] [PubMed]
- Chen, H.; Lester-Zeiner, D.; Shi, J.; Miller, S.; Glaus, C.; Hu, E.; Chen, N.; Able, J.; Biorn, C.; Wong, J.; et al. AMG 580: A novel small molecule phosphodiesterase 10A (PDE10A) positron emission tomography tracer. J. Pharmacol. Exp. Ther. 2015, 352, 327–337. [Google Scholar] [CrossRef] [PubMed]
- Hu, E.; Ma, J.; Biorn, C.; Lester-Zeiner, D.; Cho, R.; Rumfelt, S.; Kunz, R.K.; Nixey, T.; Michelsen, K.; Miller, S.; et al. Rapid identification of a novel small molecule phosphodiesterase 10A (PDE10A) tracer. J. Med. Chem. 2012, 55, 4776–4787. [Google Scholar] [CrossRef] [PubMed]
- Taniguchi, T.; Miura, S.; Hasui, T.; Halldin, C.; Stepanov, V.; Takano, A. Radiolabeled Compounds and Their Use as Radiotracers for Quantitative Imaging of Phosphodiesterase (PDE10A) in Mammals. WO 2013/027845 A1, 28 February 2013. [Google Scholar]
- Stepanov, V.; Miura, S.; Takano, A.; Amini, N.; Nakao, R.; Hasui, T.; Nakashima, K.; Taniguchi, T.; Kimura, H.; Kuroita, T.; et al. Development of a series of novel carbon-11 labeled PDE10A inhibitors. J. Label. Comp. Radiopharm. 2015, 58, 202–208. [Google Scholar] [CrossRef] [PubMed]
- Harada, A.; Suzuki, K.; Miura, S.; Hasui, T.; Kamiguchi, N.; Ishii, T.; Taniguchi, T.; Kuroita, T.; Takano, A.; Stepanov, V.; et al. Characterization of the binding properties of T-773 as a PET radioligand for phosphodiesterase 10A. Nucl. Med. Biol. 2015, 42, 146–154. [Google Scholar] [CrossRef] [PubMed]
- Takano, A.; Stepanov, V.; Gulyás, B.; Nakao, R.; Amini, N.; Miura, S.; Kimura, H.; Taniguchi, T.; Halldin, C. Evaluation of a novel PDE10A PET radioligand, [11C]T-773, in nonhuman primates: Brain and whole body PET and brain autoradiography. Synapse 2015, 69, 345–355. [Google Scholar] [CrossRef] [PubMed]
- Tóth, M.; Haggkvist, J.; Stepanov, V.; Takano, A.; Nakao, R.; Amini, N.; Miura, S.; Kimura, H.; Taniguchi, T.; Gulyas, B.; et al. Molecular imaging of PDE10A knockout mice with a novel PET radiotracer: [11C]T-773. Mol. Imaging Biol. 2015, 17, 445–449. [Google Scholar] [CrossRef] [PubMed]
- Takano, A.; Stepanov, V.; Nakao, R.; Amini, N.; Gulyás, B.; Kimura, H.; Halldin, C. Brain PET measurement of PDE10A occupancy by TAK-063, a new PDE10A inhibitor, using [11C]T-773 in nonhuman primates. Synapse 2016. [Google Scholar] [CrossRef] [PubMed]
- Kunitomo, J.; Yoshikawa, M.; Fushimi, M.; Kawada, A.; Quinn, J.F.; Oki, H.; Kokubo, H.; Kondo, M.; Nakashima, K.; Kamiguchi, N.; et al. Discovery of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (TAK-063), a highly potent, selective, and orally active phosphodiesterase 10A (PDE10A) inhibitor. J. Med. Chem. 2014, 57, 9627–9643. [Google Scholar] [CrossRef] [PubMed]
- Cox, C.D.; Hostetler, E.D.; Flores, B.A.; Evelhoch, J.L.; Fan, H.; Gantert, L.; Holahan, M.; Eng, W.; Joshi, A.; McGaughey, G.; et al. Discovery of [11C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors. Bioorg. Med. Chem. Lett. 2015, 25, 4893–4898. [Google Scholar] [CrossRef] [PubMed]
- Hostetler, E.; Cox, C.D.; Fan, H. Radiolabeled PDE10 Inhibitors. WO 2010/138577 A1, 2 December 2010. [Google Scholar]
- Raheem, I.T.; Breslin, M.J.; Fandozzi, C.; Fuerst, J.; Hill, N.; Huszar, S.; Kandebo, M.; Kim, S.H.; Ma, B.; McGaughey, G.; et al. Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia. Bioorg. Med. Chem. Lett. 2012, 22, 5903–5908. [Google Scholar] [CrossRef] [PubMed]
- Hostetler, E.D.; Fan, H.; Joshi, A.D.; Zeng, Z.; Eng, W.; Gantert, L.; Holahan, M.; Meng, X.; Miller, P.; O’Malley, S.; et al. Preclinical characterization of the phosphodiesterase 10A PET tracer [11C]MK-8193. Mol. Imaging Biol. 2015. [Google Scholar] [CrossRef] [PubMed]
- Lin, J.H.; Lu, A.Y.H. Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol. Rev. 1997, 49, 403–449. [Google Scholar] [PubMed]
- Jakobsen, S.; Kodahl, G.M.; Olsen, A.K.; Cumming, P. Synthesis, radiolabeling and in vivo evaluation of [11C]RAL-01, a potential phosphodiesterase 5 radioligand. Nucl. Med. Biol. 2006, 33, 593–597. [Google Scholar] [CrossRef] [PubMed]
Phosphodiesterase | Radioligands Review Compound No. (Code No. Given) | References |
---|---|---|
PDE2 | [18F]1 ([18F]B-23) | [48,55] |
[18F]2 ([18F]PF-05270430) | [48,56,57,58] | |
[18F]3, [18F]4, [18F]5 ([18F]TA3–5) | [60,61,62] | |
PDE4 | [18F]7 ([18F]MNI-617) | [82] |
PDE5 | [11C]8 ([11C]sildenafil), [18F]13, [11C]14, [11C]16, [11C]17 | [97] |
[18F]18 ([18F]ICF24027) | [110] | |
PDE7 | [18F]20 ([18F]MICA-003), [11C]21 ([11C]MICA-005) | [121,122] |
PDE10 | Structurally related to compound 22 (MP-10) | |
[18F]26, [11C]29 | [143] | |
[11C]30 ([11C]TZ1964B), [11C]31–33 | [157,160] | |
[18F]34–40 | [158] | |
[11C]42 | [161] | |
Structurally not derived from compound 22 (MP-10) | ||
[18F]47 ([18F]AQ28A) | [170,172] | |
[18F]48 ([18F]MNI-654), [18F]49 ([18F]MNI-659) | [175,176,177,178] | |
[11C]50 ([11C]IMA104), [11C]51 ([11C]IMA106) | [142,181] | |
[11C]52 ([11C]IMA107), [18F]53 ([18F]IMA102) | ||
[11C]54 ([11C]Lu AE92686) | [182,183] | |
[11C]55 ([11C]AMG 7980), [18F]56 ([18F]AMG 580) | [185,186,187] | |
[11C]58–60, [11C]61 ([11C]T-773), [11C]62–64 | [190,191,192,193,194] | |
[11C]66 ([11C]MK-8193), [11C]67–69 | [196,197,199] |
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Schröder, S.; Wenzel, B.; Deuther-Conrad, W.; Scheunemann, M.; Brust, P. Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012. Molecules 2016, 21, 650. https://doi.org/10.3390/molecules21050650
Schröder S, Wenzel B, Deuther-Conrad W, Scheunemann M, Brust P. Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012. Molecules. 2016; 21(5):650. https://doi.org/10.3390/molecules21050650
Chicago/Turabian StyleSchröder, Susann, Barbara Wenzel, Winnie Deuther-Conrad, Matthias Scheunemann, and Peter Brust. 2016. "Novel Radioligands for Cyclic Nucleotide Phosphodiesterase Imaging with Positron Emission Tomography: An Update on Developments Since 2012" Molecules 21, no. 5: 650. https://doi.org/10.3390/molecules21050650