Preparation and molecular modeling of radioiodopropranolol as a novel potential radiopharmaceutical for lung perfusion scan
Objective: Development of easy method for radioiodination of propranolol with high percent labeling yield for the purpose of lung perfusion imaging.
Methods: Radioidination of propranolol was achieved using 125I via electrophilic substitution under the oxidative conditions of cholramine-T (CAT). All factors affecting the labeling procedure and labeling yield were studied. Paper electrophoresis and HPLC were performed to determine the radiochemical yield and purity of the 125I-propranolol. Molecular modeling and docking studies were performed to ensure the binding of the newly obtained 125I-propranolol to beta-2 (Î²2) adrenergic receptor.
Results: Radioiodination of propranolol has been successfully achieved with high labeling yield (93.7 Â± 0.81% ) . 125I-propranolol was stable for 24 h when kept in dark at ambient temperature. Biodistribution studies showed lung uptake of 21.60 Â± 0.03% injected dose/g Â (%ID/g) at 30 min post-injection. Molecular modeling confirmed that radioiodination did not affect the binding of propranolol to Î²2- receptor.
Conclusion: Iodopropranolol can be considered as good potential lung perfusion agent as suggested by the results of biodistribution and molecular modeling studies.
2. Cooper DS, Doherty GM, Haugen BR, Kloos RT, LeeSL, Mandel SJ, et al. Management guidelines for patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association Guidelines Taskforce. Thyroid 2006;16:109-142.
3. Al-Saeedi FJ. Perfusion scanning using 99mTc-HMPAO detects early cerebrovascular changes in the diabemtic rat, BMC medical physics 2008;8:1-4.
4.Motaleb MA, El-Kolaly MT, Rashed HM, El-Bary AA, Radioiodinated paroxetine, a novel potential radiopharmaceutical for lung perfusion scan. J Radioanal Nucl Chem. 2011;292:629-635.
5.Thieme SF, Johnson TR, Reiser MF, Nikolaou K. Dual-Energy Lung Perfusion Computed Tomography: A Novel Pulmonary Functional Imaging Method. J Seminars in ultrasound, CT, and MR 2010;31:301-308.
6.Miroslavov AE, Gorshkov NI, Lumpov AL, Yalfimov AN, Suglobov DN, Ellis BL, et al. Evaluation of 99mTc(CO)5I as a potential lung perfusion agent. Nucl Med Biol 2009;36:73-79.
7. De K, Chandra , Sarkar B, Ganguly S, Misra M. Synthesis and biological evaluation of 99mTc-DHPM complex: a potential new radiopharmaceutical for lung imaging studies. J Radioanal Nucl Chem 2010;83:621-628.
8.Rashed HM, Ibrahim IT, Motaleb MA, El-Bary AA. Preparation of radioiodinated ritodrine as a potential agent for lung imaging, J Radioanal Nucl Chem 2014;300:1227-1233.
9.Burger A, Abraham DJ. Burger's medicinal chemistry and drug discovery: Cardiovascular agents and endocrined. Wiley. New York;2003.
10.Kadam SS, Mahadik KR, Bothara KG. Principles of medicinal chemistry. Nirali Prakashan, Mumbai;2010.
11.Greenwood NN, Earnshaw A. Chemistry of the Elements. Elsevier Butterworth-Heinmann, Oxford; 1997.
12.Patel BN, Doshi AK, Patel CN. RP-HPLC method for simultaneous estimation of propranolol hydrochloride and flunarizine dihydrochloride in their combined dosage formulation. Chronicles of Young Scientists 2012;3:274-278.
13.Wagener FA, Eggert A, Boerman OC, Oyen WJ, Verhofstad A, Abraham NG, et al. Heme is a potent inducer of inflammation in mice and is counteracted by heme oxygenase, Blood 2001; 98:1802-1811.
14.Hoffman TJ, Gali H, Smith CJ, Sieckman GL, Hayes DL, Owen NK, Volkert WA. Novel series of 111In-labeled bombesin analogs as potential radiopharmaceuticals for specific targeting of gastrin-releasing peptide receptors expressed on human prostate cancer cells. J Nul Med 2003;44(5):823-831.
15.Baker JG, Proudman RG, Hawley NC, Fischer PM, Hill SJ. Role of key transmembrane residues in agonist and antagonist actions at the two conformations of the human beta1-adrenoceptor. Mol Pharmacol 2008;74:1246-1260.
16.El-Azony KM, Preparation of 125I -celecoxib with high purity as a possible tumor agent J Radioanal Nucl Chem 2010;285:315â€“320.
17.Coenen HH, Mertens J, Mazie're B. Radioiodination Reactions For Pharmaceuticals: Compendium for Effective Synthesis Strategies. Springer. The Netherlands; 2006.
18.Sukhdev A, Shubha JP. Kinetics and reactivities of ruthenium (III)-and osmium (VIII)-catalyzed oxidation of ornidazole with chloramine-T in acid and alkaline media: A mechanistic approach. J Mol Cat. A Chem 2009;310(1):24-33.
19.Chetty P. Development and assessment of propranolol sustained release dosage forms separately and in combination with hydrochlorothiazide. Master of science. Rhodes University; 2006.
20.FA C. Cotton, Wilkinson G , Advanced inorganic chemistry. Wiley. New York;1998.
21. Amin AM, El-bary AA, El-Mohty AA, Saad SM, El-Sharawy DM, Radioiodination and biological evaluation of valsartan as a tracer for cardiovascular disorder detection. Natural Science 2013;5(4):526-531.
22. Nishijima K, Kuge Y, Motoki N, Seki K, Ohkura K, Morita K, Tamaki N. In vitro and in vivo characterization of high specific activity S-(-)[11C]CGP-12177, a radioligand for Î²-adrenoreceptor, in rats. International Congress Series 2004;1264:261-266.
23.van Waarde A, Meeder JG, Blanksma PK, Bouwer J, Visser GM, Elsinga PH, et al. Suitability of CGP-12177 and CGP-26505 for quantitative imaging of beta-adrenoceptors. Int J Rad Appl Instrum B 1992;19:711-718.
24. Farahati J, Bier D, Scheubeck M, Lassmann M, Schelper LF, Grelle I, et al. Effect of specific activity on cardiac uptake of iodine-123-MIBG, J Nucl Med 1997;38(3), 447-450.
25. Shand DG. Pharmacokinetics of propranolol: a review. Postgraduate medical journal 1975;52:22-25.
26. B. Mehta, M. Mehta, Organic Chemistry .Prentice-Hall of India Pvt.Ltd. India;2005.