Radiolabeling, docking studies on in silico ADME and biological evaluation of serotonin with <sup>125</sup>I for 5-HTR imaging

Dina M. El-Sharawy; Marwa S. El Refaye; H. Hussein; Asmaa M. AboulMagd

doi:10.1007/s41365-020-00784-9

Your Location：

Home >

Browse articles >

Radiolabeling, docking studies on in silico ADME and biological evaluation of serotonin with ¹²⁵I for 5-HTR imaging

NUCLEAR CHEMISTRY, RADIOCHEMISTRY, RADIOPHARMACEUTICALS AND NUCLEAR MEDICINE | Updated：2021-01-26

- Radiolabeling, docking studies on in silico ADME and biological evaluation of serotonin with ¹²⁵I for 5-HTR imaging
- Nuclear Science and Techniques Vol. 31, Issue 8, Article number: 80(2020)
- Affiliations：
  
  1.Labeled Compounds Department, Hot Lab. Center, Egyptian Atomic Energy Authority (EAEA), P.O. Box 13759, Cairo, Egypt
  2.Radioactive Isotopes and Generators Department, Hot Lab. Center, Egyptian Atomic Energy Authority (EAEA), P.O. Box 13759, Cairo, Egypt.
  3.Cyclotron Project, Nuclear Research Centre
  4.Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni Suef, Egypt
  5.Pharmaceutics and Clinical Pharmacy Department, Faculty of Pharmacy, Nahda University, Beni Suef, Egypt
- Author bio：
  
  Corresponding authors: dina.sharawy@nub.edu.eg;
  asmaa.aboulmaged@nub.edu.eg
- Funds：
- DOI：10.1007/s41365-020-00784-9
  CLC：
Scan for full text
Dina M. El-Sharawy, Marwa S. El Refaye, H. Hussein, et al. Radiolabeling, docking studies on in silico ADME and biological evaluation of serotonin with ¹²⁵I for 5-HTR imaging. [J]. Nuclear Science and Techniques 31(8):80(2020)
DOI：

Dina M. El-Sharawy, Marwa S. El Refaye, H. Hussein, et al. Radiolabeling, docking studies on in silico ADME and biological evaluation of serotonin with ¹²⁵I for 5-HTR imaging. [J]. Nuclear Science and Techniques 31(8):80(2020) DOI： 10.1007/s41365-020-00784-9.

摘要

Abstract

Serotonin is one of the significant signaling molecules used by several neural systems in the gut and brain. This study aimed to develop a novel and potent tracer for targeting, detecting, and imaging serotonin receptors (5-HTRs), which is a promising tool in the determination of the receptor’s function and relationship with the diseases related to serotonin and it’s receptor dysfunction.. Serotonin was effectively labeled via a direct electrophilic substitutional reaction using an oxidizing agent such as iodogen with,125,I in a neutral medium, and ,125,I-serotonin was achieved with a maximum labeling yield of 91 ± 0.63% with in vitro stability up to 24 h. Molecular modeling was conducted to signify ,125,I-serotonin structure and confirm that the radiolabeling process did not affect serotonin binding ability to its receptors. Biodistribution studies show that the maximum gastro intestinal tract Gastro Intestinal Tract (GIT) uptake of ,125,I-serotonin was 17.8 ± 0.93% ID/organ after 30 min post-injection and the tracer’s ability to pass the blood-brain barrier. Thus,125,I-serotonin is a promising single photon emmision computed tomography Single Photon Emission Computed Tomography (SPECT) tracer in the detection of 5HTRs.

关键词

Keywords

SerotoninElectrophilic substitutionMolecular modeling5HTRs

references

Z. Li, A. Chalazonitis, Y.Y. Huang et al. Essential roles of enteric neuronal serotonin in gastrointestinal motility and the development/survival of enteric dopaminergic neurons. J Neurosci. 31, 8998-9009. (2011). https://doi.org/10.1523/JNEUROSCI.6684-10https://doi.org/10.1523/JNEUROSCI.6684-10

N. Terry, K.G. Margolis. Serotonergic Mechanisms Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance. Handb Exp Pharmacol.239, 319-342.(2017). https://doi.org/10.1007/164_2016_103https://doi.org/10.1007/164_2016_103

K.O. Grønstad, L. DeMagistris, A. Dahlström et al. The effects of vagal nerve stimulation on endoluminal release of serotonin and substance P into the feline small intestine. J Scand Gastroenterol. 20, 163-169 (1985) https://doi.org/10.3109/00365528509089650https://doi.org/10.3109/00365528509089650

J. J. Chen, L.I. Zhishan, H. Pan, et al. Maintenance of Serotonin in the Intestinal Mucosa and Ganglia of Mice that Lack the High-Affinity Serotonin Transporter: Abnormal Intestinal Motility and the Expression of Cation Transporters. J Neurosci 21, 6348-6361.(2001). https://doi.org/10.1523/JNEUROSCI.21-16-06348https://doi.org/10.1523/JNEUROSCI.21-16-06348.

E. Bülbring, A. Creema. The release of 5-hydroxytryptamine in relation to pressure exerted on the intestinal mucosa. J Physiol. 146,18-28(1959).https://doi.org/10.1113/jphysiol.1959.sp006175https://doi.org/10.1113/jphysiol.1959.sp006175

P.P Bertrand. Real-time detection of serotonin release from enterochromaffin cells of the guinea- pig ileum. Neurogastroenterol Motil. 16,511-514(2004). https://doi.org/10.1111/j.1365-2982.2004.00572.xhttps://doi.org/10.1111/j.1365-2982.2004.00572.x

H. Schwörer, K. Racké, H. Kilbinger. Cholinergic modulation of the release of 5-hydroxtryptamine from the guinea pig ileum. Naunyn-Schmiedeberg’s Arch Pharmacol. 336, 127-132 (1987). https://doi.org/10.1007/BF00165795https://doi.org/10.1007/BF00165795

K. Racké, A. Reimann, H. Schwörer, et al. Regulation of 5-HT release from enterochromaffin cells. Behav Brain Res. 73, 83-87 (1996). https://doi.org/10.1016/0166-4328(96)00075-7https://doi.org/10.1016/0166-4328(96)00075-7

M.D. Gershon, Nerves reflexes and the enteric nervous system: pathogenesis of the irritable bowel syndrome. J Clin Gastroenterol. 39,184-193 (2005).https://doi.org/10.1097/01.mcg.0000156403.37240.30https://doi.org/10.1097/01.mcg.0000156403.37240.30

V. Erspamer. Occurrence of indolealkylamines in nature. Handbook of experimental pharmacology. Springer-Verlag: New York. 19, 132-181(1966)

M.D. Gershon, The Serotonin Signaling System: From Basic Understanding To Drug Development for Functional GI Disorders. J Gastroenterology, 132, 397-414 (2007). https://doi.org/10.1053/j.gastro.2006.11.002https://doi.org/10.1053/j.gastro.2006.11.002

M.D. Gershon. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Curr Opin Endocrinol Diabetes Obes.20,14-21. (2013). https://doi.org/10.1097/MED.0b013e32835bc703https://doi.org/10.1097/MED.0b013e32835bc703

M. Vialli. Histology of the enterochromaffin cell system. Handbook of experimental pharmacology. Springer-Verlag, New York. 19, 1-65(1966)

L. Lemoine, J. Andries, D.L. Bars, et al. Comparison of 4 Radiolabeled Antagonists for Serotonin 5-HT7 Receptor Neuroimaging: Toward the First PET Radiotracer, J Nucl Med. 52, 1811-1818 (2011). https://doi.org/10.2967/jnumed.111.089185https://doi.org/10.2967/jnumed.111.089185.

B. Vidal, S. Fieux, M. Colom, et al. 18F-F13640 preclinical evaluation in rodent, cat and primate as a 5-HT1A receptor agonist for PET neuroimaging. Brain Structure and Function. 223, 2973-2988(2018). https://doi.org/10.1007/s00429-018-1672-7https://doi.org/10.1007/s00429-018-1672-7

L.M. Paterson, B.R. Kornum, D.J. Nutt, et al. 5-HT radioligands for human brain imaging with PET and SPECT. Med Res Rev. 33, 54-111 (2013). https://doi.org/10.1002/med.20245https://doi.org/10.1002/med.20245.

G.B. Meerveld, K. Venkova, G. Hicks, et al. Activation of peripheral 5-HT receptors attenuates colonic sensitivity to intraluminal distension. Neurogastroenterol Motil. 18, 76-86 (2006). https://doi.org/10.1111/j.1365-2982.2005.00723.xhttps://doi.org/10.1111/j.1365-2982.2005.00723.x

L.M. Paterson, R.J Tayak, D.J. Nutt, et al. Measuring endogenous 5-HT release by emission tomography: promises and pitfalls. J Cereb Blood Flow Metab.30,1682-706 (2010). https://doi.org/10.1038/jcbfm.2010.104https://doi.org/10.1038/jcbfm.2010.104.

S. N. Farrag, A. Hanan. E.M. Abdulaziz. et al. Comparative study on radiolabeling and biodistribution of core-shell silver/polymeric nanoparticles-based theranostics for tumor targeting, International J of Pharmaceutics. 529,123-133 (2017).https://doi.org/10.1016/j.ijpharm.2017.06.044https://doi.org/10.1016/j.ijpharm.2017.06.044

F. Côté, E. Thévenot, C. Fligny, et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc Natl Acad Sci USA. 100, 13525-13530 (2003). https://doi.org/10.1073/pnas.2233056100https://doi.org/10.1073/pnas.2233056100

S. N. Farrag, A.O. Abdel Moamen, Facile radiolabeling optimization process via design of experiments and an intelligent optimization algorithm: Application for omeprazole radioiodination, J Label Compd Radiopharm. 62, 280-287 (2019). https://doi.org/10.1002/jlcr.3734https://doi.org/10.1002/jlcr.3734

M.A. Motaleb, M.T. El-Kolaly, H.M. Rashed, et al. Radioiodinated paroxetine, a novel potential radiopharmaceutical for lung perfusion scan, J Radioanal Nucl Chem. 292, 629-635 (2012). https://doi.org/10.1007/s10967-011-1499-7https://doi.org/10.1007/s10967-011-1499-7

J. Thomas, R. Khanam, D. Vohora, A validated HPLC-UV method and optimization of sample preparation technique for norepinephrine and serotonin in mouse brain. J Pharmaceutical Biology.53,1539-1544 (2015).https://doi.org/10.3109/13880209.2014.991837https://doi.org/10.3109/13880209.2014.991837

M.H. Sanad, M. El-Tawoosy, Labeling of ursodeoxycholic acid with technetium-99m for hepatobiliary imaging, J Radioanal Nucl Chem. 298, 1105-1109.(2013). https://doi.org/10.1007/s10967-013-2512-0https://doi.org/10.1007/s10967-013-2512-0

B. S. Challan, A. Massoud, Radiolabeling of graphene oxide by Tchnetium-99m for infection imaging in rats, J Radioanal Nucl Chem. 314, 2189-2199 (2017). https://doi.org/10.1007/s10967-017-5561-yhttps://doi.org/10.1007/s10967-017-5561-y

T. Sharma, L.S. Guski,N. Freund, et al. Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports. BMJ. 352:i65.(2016). https://doi.org/10.1136/bmj.i65https://doi.org/10.1136/bmj.i65

A. M. Amin, N. S. Farrag and A. AbdEl-Bary, Iodine-125-Chlorambucil as Possible Radio Anticancer for Diagnosis and Therapy of Cancer: Preparation and Tissue Distribution, B J P R. 4 1873-1885 (2014). https://doi.org/10.9734/BJPR/2014/10520https://doi.org/10.9734/BJPR/2014/10520

A.M. Amin, A. Abd El-Bary, M. Shoukry, Study of the conditions for ibuprofen labeling with 125I to prepare an inflammation imaging agent, J Radiochemistry. 55, 615-619 (2013). https://doi.org/10.1134/S106636221306009Xhttps://doi.org/10.1134/S106636221306009X

K.M. El-Azony, A.A. El-Mohty, H.M. Killa, et al. An investigation of the 125I-radioiodination of colchicine for medical purposes. J Labelled Compds. Radiopharm.52: 1-3 (2008). https://doi.org/10.1002/jlcr.1556https://doi.org/10.1002/jlcr.1556

K. El-Azony. Preparation of 125 I-celecoxib with high purity as a possible tumor agent. J. of Radioanal. Nucl. Chem. 285,315-320 (2010). https://doi.org/10.1007/s10967-010-0583-8https://doi.org/10.1007/s10967-010-0583-8

A. Braganza, W.O. Wilson. Elevated temperature effects on catecholamines and serotonin in brains of male Japanese quail., J Appl Physiol Respir Environ Exerc Physiol.45:705-708 (1978). https://doi.org/10.1152/jappl.1978.45.5.705https://doi.org/10.1152/jappl.1978.45.5.705

B.M. Essa, T.M. Sakr, M.A. Khedr, et al. 99mTc-amitrol as a novel selective imaging probe for solid tumer: in Silico and preclinical pharmacological study. J Eur Pharm Sci. 76,102-109 (2015). https://doi.org/10.1016/j.ejps.2015.05.002https://doi.org/10.1016/j.ejps.2015.05.002

E.J. Knust, K. Dutschk, Radiopharmaceutical preparation of 3-123I-α-methyltyrosine for nuclearmedical applications, J of Radioannal Nucl Chem. 144,107-113.(1990)

H. M. Rashed, I. T. Ibrahim, M. A. Motaleb, A. Abd El-Bary, Preparation of radioiodinated ritodrine as a potential agent for lung imaging, J Radioanal Nucl Chem 300:1227-1233 (2014). https://doi.org/10.1007/s10967-014-3077-2https://doi.org/10.1007/s10967-014-3077-2

S. G-Deniau, A.F. Burnol and J. Girard, Identification and Localization of a Skeletal Muscle Secrotonin 5-HT2A Receptor Coupled to the Jak/STAT Pathway, J of Biological Chemistry 272, 14825-14829.(1997). https://doi.org/10.1074/jbc.272.23.14825https://doi.org/10.1074/jbc.272.23.14825

N. R. Waterhouse. Determination of lipophilicity and its use as a predictor of blood-brain barrier penetration of molecular imaging agents, Molecular Imaging & Biology. 5, 376-89. (2003). https://doi.org/10.1016/j.mibio.2003.09.014https://doi.org/10.1016/j.mibio.2003.09.014

Y.H. Zhao, M.H. Abraham. Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure-activity relationship (QSAR) with the Abraham descriptors, J Pharm. Sci. 90, 749-784 (2001) https://doi.org/10.1002/jps.1031https://doi.org/10.1002/jps.1031

T.J. Hou, W. Zhang. ADME evaluation in drug discovery. Correlation of caco-2 permeation with simple molecular properties, J Chem. Inf. Comput. Sci. 44, 1585-1600 (2004). https://doi.org/10.1021/ci049884mhttps://doi.org/10.1021/ci049884m.

Y.C. Chang, C.P. Chen, C.C. Chen. 2012 International Symposium on Safety Science and Technology Predicting skin permeability of chemical substances using a quantitative structure-activity relationship, Procedia Engineering, 45, 875-879 (2012). https://doi.org/10.1016/j.proeng.2012.08.252https://doi.org/10.1016/j.proeng.2012.08.252.

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

No data

Related Author

No data

Related Institution

No data

Address：Editorial Office of NST, 2019 Jialuo Road, Jiading, Shanghai 201800, China Postal code：201800
Email：nst@sinap.ac.cn
Technical support is provided by Beijing Founder electronics co., LTD 沪ICP备05005479号-1 京公网安备11010802024621
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Radiolabeling, docking studies on in silico ADME and biological evaluation of serotonin with 125I for 5-HTR imaging

DOI：10.1007/s41365-020-00784-9

摘要

Abstract

关键词

Keywords

references

Radiolabeling, docking studies on in silico ADME and biological evaluation of serotonin with ¹²⁵I for 5-HTR imaging