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Current Radiopharmaceuticals

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ISSN (Print): 1874-4710
ISSN (Online): 1874-4729

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Research Article

Radiolabeling of Zonisamide for a Diagnostic Perspective

Author(s): Emine Dervis, Kadriye Busra Karatay, Kubra Durkan* and Ayfer Yurt Kilcar

Volume 17, Issue 1, 2024

Published on: 10 October, 2023

Page: [91 - 98] Pages: 8

DOI: 10.2174/0118744710249156231002115024

Price: $65

Abstract

Objective: Epilepsy is one of the oldest and the most common chronic neurological diseases. Antiepileptic drugs (AEDs) are the backbone of epilepsy treatment. However, epileptogenesis has not been fully elucidated. One of the critical reasons for this is the lack of reliable biomarkers. Neuroimaging suggests a non-invasive examination and investigation tool that can detect critical pathophysiological changes involved in epileptogenesis and monitor disease progression. In the current study, the radiolabeling potential of Zonisamide (ZNS) (the secondgeneration AED) with Technetium-99m (99mTc) is examined to neuroimage the epileptogenic processes by contributing to the development of potential radiotracers.

Methods: ZNS was labeled with 99mTc and the radiochemical yield of [99mTc]Tc-ZNS was determined with TLRC (Thin Layer Liquid Radio Chromatography and HPLRC (High Performance Liquid Radio Chromatography) radiochromatographic methods. In vitro behavior of [99mTc]Tc-ZNS was determined with time-dependent uptake of [99mTc]Tc-ZNS on the SHSY5Y human neuroblastoma cells.

Results: The radiochemical yield of [99mTc]Tc-ZNS was determined as 98.03 ± 1.24% (n = 6) according to radiochromatographic studies results. [99mTc]Tc-ZNS demonstrated 5.38 and 6.18 times higher uptake values than the control group on the human neuroblastoma SH-SY5Y cell line at 120 and 240 minutes, respectively.

Conclusion: This study showed that the current radiolabeled antiepileptic drug has a diagnostic potential to be used in imaging neurological processes.

Keywords: Zonisamide (ZNS), antiepileptic drugs, epilepsy, technetium-99m (99mTc), neuroimaging, in vitro.

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[1]
Brusa, R.; Zimmermann, F.; Koh, D.S. Early-onset epilepsy and postnatal lethality associated with an editing-deficient glur-B allele in mice. Science, 1995, 270, 1677-1680.
[http://dx.doi.org/10.1126/science.270.5242.1677]
[2]
Shultz, S.R.; O’Brien, T.J.; Stefanidou, M.; Kuzniecky, R.I. Neuroimaging the epileptogenic process. Neurotherapeutics, 2014, 11(2), 347-357.
[http://dx.doi.org/10.1007/s13311-014-0258-1] [PMID: 24488707]
[3]
Patsalos, P.N.; Spencer, E.P.; Berry, D.J. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: A 2018 update. Ther. Drug Monit., 2018, 40(5), 526-548.
[http://dx.doi.org/10.1097/FTD.0000000000000546] [PMID: 29957667]
[4]
Sankaraneni, R.; Lachhwani, D. Antiepileptic drugs-a review. Pediatr. Ann., 2015, 44(2), e36-e42.
[http://dx.doi.org/10.3928/00904481-20150203-10] [PMID: 25658217]
[5]
Baker, G.A.; Jacoby, A.; Buck, D.; Stalgis, C.; Monnet, D. Quality of life of people with epilepsy: a European study. Epilepsia, 1997, 38(3), 353-362.
[http://dx.doi.org/10.1111/j.1528-1157.1997.tb01128.x] [PMID: 9070599]
[6]
Schauf, C.L. Zonisamide enhances slow sodium inactivation inMyxicola. Brain Res., 1987, 413(1), 185-188.
[http://dx.doi.org/10.1016/0006-8993(87)90168-5] [PMID: 2439177]
[7]
Hitiris, N.; Mohanraj, R.; Norrie, J.; Sills, G.J.; Brodie, M.J. Predictors of pharmacoresistant epilepsy. Epilepsy Res., 2007, 75(2-3), 192-196.
[http://dx.doi.org/10.1016/j.eplepsyres.2007.06.003] [PMID: 17628429]
[8]
Brodie, M.J.; Ben-Menachem, E.; Chouette, I.; Giorgi, L. Zonisamide: its pharmacology, efficacy and safety in clinical trials. Acta Neurol. Scand., 2012, 126(194), 19-28.
[http://dx.doi.org/10.1111/ane.12016] [PMID: 23106522]
[9]
Vajda, F.J.E. New antiepileptic drugs. J. Clin. Neurosci., 2000, 88-101.
[10]
Erdogan, F.F. New antiepileptic drugs. J Turkish Epilepsi Soc., 2014, 20, 56-58.
[11]
Leppik, I.E. Zonisamide: Chemistry, mechanism of action, and pharmacokinetics. Seizure, 2004, 13(Suppl. 1), S5-S9.
[http://dx.doi.org/10.1016/j.seizure.2004.04.016] [PMID: 15511691]
[12]
Yamamura, S.; Hamaguchi, T.; Ohoyama, K.; Sugiura, Y.; Suzuki, D.; Kanehara, S.; Nakagawa, M.; Motomura, E.; Matsumoto, T.; Tanii, H.; Shiroyama, T.; Okada, M. Topiramate and zonisamide prevent paradoxical intoxication induced by carbamazepine and phenytoin. Epilepsy Res., 2009, 84(2-3), 172-186.
[http://dx.doi.org/10.1016/j.eplepsyres.2009.01.015] [PMID: 19268540]
[13]
Yamamura, S.; Ohoyama, K.; Nagase, H.; Okada, M. Zonisamide enhances delta receptor-associated neurotransmitter release in striato-pallidal pathway. Neuropharmacology, 2009, 57(3), 322-331.
[http://dx.doi.org/10.1016/j.neuropharm.2009.05.005] [PMID: 19482038]
[14]
Sano, H.; Nambu, A. The effects of zonisamide on L-DOPA–induced dyskinesia in Parkinson’s disease model mice. Neurochem. Int., 2019, 124, 171-180.
[http://dx.doi.org/10.1016/j.neuint.2019.01.011] [PMID: 30639196]
[15]
Nabati, M.; Bodaghi-Namileh, V. Design of Novel Drugs (P3TZ, H2P3TZ, M2P3TZ, H4P3TZ and M4P3TZ) Based on Zonisamide for Autism Treatment by Binding to Potassium Voltage-gated Channel Subfamily D Member 2 (Kv4.2). Int. J. New. Chem., 2019, 6, 254-276.
[16]
Greiner-Sosanko, E.; Giannoutsos, S.; Lower, D.R.; Virji, M.A.; Krasowski, M.D. Drug monitoring: simultaneous analysis of lamotrigine, oxcarbazepine, 10-hydroxycarbazepine, and zonisamide by HPLC-UV and a rapid GC method using a nitrogen-phosphorus detector for levetiracetam. J. Chromatogr. Sci., 2007, 45(9), 616-622.
[http://dx.doi.org/10.1093/chromsci/45.9.616] [PMID: 17988451]
[17]
Reddy, K.A. Determination of zonisamide in capsule dosage form by using RP-HPLC. Int. J. Chem. Sci., 2011, 9, 1698-1704.
[18]
Yeniceli, D. Development and validation of a simple and efficient HPLC method for the determination of zonisamide in pharmaceuticals and human plasma. J. Anal. Chem., 2013, 68(5), 436-443.
[http://dx.doi.org/10.1134/S1061934813050080]
[19]
Yurt Kilcar, A.; Tekin, V.; Biber Muftuler, F.Z.; Medine, E.I. 99mTc labeled plumbagin: estrogen receptor dependent examination against breast cancer cells and comparison with PLGA encapsulated form. J. Radioanal. Nucl. Chem., 2016, 308(1), 13-22.
[http://dx.doi.org/10.1007/s10967-015-4284-1]
[20]
Zolle, I. Technetium-99m pharmaceuticals preparation and quality. 2007, 173-337.
[21]
Saha, GB Fundamentals of Nuclear Pharmacy; SpringerLink, 2010.
[http://dx.doi.org/10.1007/978-1-4419-5860-0]
[22]
Park, K.M.; Lee, B.I.; Shin, K.J.; Ha, S.Y.; Park, J.; Kim, S.E.; Kim, S.E. Efficacy, tolerability, and blood concentration of zonisamide in daily clinical practice. J. Clin. Neurosci., 2019, 61, 44-47.
[http://dx.doi.org/10.1016/j.jocn.2018.11.012] [PMID: 30446366]
[23]
Kovalevich, J.; Langford, D. Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods Mol. Biol., 2013, 1078, 9-21.
[http://dx.doi.org/10.1007/978-1-62703-640-5_2] [PMID: 23975817]
[24]
Han, X.; Zhu, S.; Wang, B.; Chen, L.; Li, R.; Yao, W.; Qu, Z. Antioxidant action of 7,8-dihydroxyflavone protects PC12 cells against 6-hydroxydopamine-induced cytotoxicity. Neurochem. Int., 2014, 64, 18-23.
[http://dx.doi.org/10.1016/j.neuint.2013.10.018] [PMID: 24220540]
[25]
Yang, L.; Rieves, D.; Ganley, C. Brain amyloid imaging--FDA approval of florbetapir F18 injection. N. Engl. J. Med., 2012, 367(10), 885-887.
[http://dx.doi.org/10.1056/NEJMp1208061] [PMID: 22931256]
[26]
Ocak, M. Radiopharmaceuticals for pet. Toraks Cerrahisi Bulteni, 2015, 6(2), 154-160.
[http://dx.doi.org/10.5152/tcb.2015.056]
[27]
Fro, H.; Inoue, K.; Goto, R.; Kinomura, S.; Taki, Y.; Okada, K.; Sato, K.; Sato, T.; Kanno, I.; Fukuda, H. Database of normal human cerebral blood flow measured by SPECT: I. Comparison between I-123-IMP, Tc-99m-HMPAO, and Tc-99m-ECD as referred with O-15 labeled water PET and voxel-based morphometry. Ann. Nucl. Med., 2006, 20(2), 131-138.
[http://dx.doi.org/10.1007/BF02985625] [PMID: 16615422]
[28]
Inoue, K.; Nakagawa, M.; Goto, R.; Kinomura, S.; Sato, T.; Sato, K.; Fukuda, H. Regional differences between 99m Tc-ECD and 99m Tc-HMPAO SPET in perfusion changes with age and gender in healthy adults. Eur. J. Nucl. Med. Mol. Imaging, 2003, 30(11), 1489-1497.
[http://dx.doi.org/10.1007/s00259-003-1234-x] [PMID: 14579088]
[29]
FDA, cder. ZONEGRAN® (zonisamide) capsules, for oral administration. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020789s036lbl.pdf
[30]
Mimaki, T.; Suzuki, Y.; Tagawa, T.; Tanaka, J.; Itoh, N.; Yabuuchi, H. [3H]zonisamide binding in rat brain. Jpn. J. Psychiatry Neurol., 1988, 42(3), 640-642.
[PMID: 2853808]
[31]
Li, L.; Rousseau, J.; Jaraquemada-Peláez, M.G.; Wang, X.; Robertson, A.; Radchenko, V.; Schaffer, P.; Lin, K.S.; Bénard, F.; Orvig, C. 225Ac-H4 py4pa for targeted alpha therapy. Bioconjug. Chem., 2021, 32(7), 1348-1363.
[http://dx.doi.org/10.1021/acs.bioconjchem.0c00171] [PMID: 32216377]
[32]
Ku, A.; Facca, V.J.; Cai, Z. Auger electrons for cancer therapy – a review. EJNMMI Radiopharm. Chem., 2019, 4(1), 27.
[http://dx.doi.org/10.1186/s41181-019-0075-2]

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