Journal of Radioanalytical and Nuclear Chemistry

, Volume 314, Issue 2, pp 1297–1307 | Cite as

99mTc-hexoprenaline and 131I-dapoxetine: preparation, in silico modeling and biological evaluation as promising lung scintigraphy radiopharmaceuticals

  • H. M. Rashed
  • I. T. Ibrahim
  • M. A. Motaleb


Hexoprenaline and dapoxetine (two lung selective pharmaceutical compounds) were radiolabeled to produce lung imaging radiopharmaceuticals using 99mTc and 131I, respectively. Different factors affecting labeling process were examined and optimum radiochemical purities of 91.3 ± 0.294 and 96.5 ± 0.342% were obtained, respectively. In silico molecular modeling studies for 99mTc-hexoprenaline and 131I-dapoxetine were done. Molecular modeling studies of the radiolabeled compounds examined the effect of radiolabeling on structure activity relationship for hexoprenaline and dapoxetine. Biodistribution studies in Swiss albino mice showed poor lung uptake of 99mTc-hexoprenaline and high uptake for 131I-dapoxetine (15.26 ± 0.11 and 55.82 ± 0.201%ID/g, respectively) matching the molecular modeling expectations. Consequently, 131I-dapoxetine could be a hopeful radiopharmaceutical for lung scintigraphic imaging and further studies to radiolabel hexoprenaline with 131I are recommended.


Hexoprenaline Dapoxetine Radiolabeling Molecular modeling Lung imaging radiopharmaceuticals 



Authors highly acknowledge Assist. Lecturer Mona O. Sarhan for her great help in the molecular modeling studies.

Compliance with ethical standards

Conflict of interest

The authors report no declarations of interest.


  1. 1.
    Saha GB (2010) Fundamentals of nuclear pharmacy, 6th edn. Springer, New YorkCrossRefGoogle Scholar
  2. 2.
    Minoshima Satoshi, Cross Donna, Wang Angela, Foster Norman, Drzezga Alexander (2016) Peak location of amyloid PET tracer uptake within cortical gray matter: topographic Patterns and diagnostic application in Alzheimer’s disease. J Nucl Med 57:512CrossRefGoogle Scholar
  3. 3.
    Sakr TM, Moustapha ME, Motaleb MA (2013) 99mTc-nebivolol as a novel heart imaging radiopharmaceutical for myocardial infarction assessment. J Radioanal Nucl Chem 295(2):1511–1516CrossRefGoogle Scholar
  4. 4.
    He Wei, Zhai Weihao, Avondo Jerome (2016) The clinical value of novel hybrid 3D lobar quantification SPECT Lung ventilation/perfusion scan in predicting remaining lung function for lobectomy lung cancer patients. J Nucl Med 57:244Google Scholar
  5. 5.
    Bartalena T, Oboldi D, Guidalotti PL, Rinaldi MF, Bertaccini P, Napoli G, Gavelli G (2008) Lung perfusion in patients with pulmonary hypertension: comparison between MDCT pulmonary angiography with minIP reconstructions and 99 mTc-MAA perfusion scan. Invest Radiol 43:368–373CrossRefGoogle Scholar
  6. 6.
    Zöphel K, Bacher-Stier C, Pinkert J, Kropp J (2009) Ventilation/perfusion lung scintigraphy: what is still needed? A review considering technetium-99m-labeled macro-aggregates of albumin. Ann Nucl Med 23:1–16CrossRefGoogle Scholar
  7. 7.
    Vijayvergiya R, Mittal BR, Grover A, Hariram V, Bhattacharya A, Singh B (2009) Assessment of IVC filter efficacy in prevention of pulmonary thromboembolism by 99mTc-MAA lung perfusion scintigraphy—a case series and review of literature. Int J Cardiol 133:122–125CrossRefGoogle Scholar
  8. 8.
    Miroslavov AE, Gorshkov NI, Lumpov AL, Yalfimov AN, Suglobov DN, Ellis BL, Braddock R, Smith AM, Prescott MC, Lawson RS, Sharma HL (2009) Evaluation of 99mTc(CO)5I as a potential lung perfusion agent. Nucl Med Biol 36:73–79CrossRefGoogle Scholar
  9. 9.
    Swidan MM, Sakr TM, Motaleb MA, Abd El-Bary A, El-Kolaly MT (2015) Preliminary assessment of radioiodinated fenoterol and reproterol as potential scintigraphic agents for lung imaging. J Radioanal Nucl Chem 303(1):531–539CrossRefGoogle Scholar
  10. 10.
    De K, Chandra S, Sarkar B, Ganguly S, Misra M (2010) Synthesis and biological evaluation of 99mTc-DHPM complex: a potential new radiopharmaceutical for lung imaging studies. J Radioanal Nucl Chem 283:621–628CrossRefGoogle Scholar
  11. 11.
    Sakr TM (2014) Synthesis and preliminary affinity testing of 123I/125I-N-(3-Iodophenyl)-2 methylpyrimidine-4,6-diamine as a novel potential lung scintigraphic agent. Radiochemistry 56(2):200–206CrossRefGoogle Scholar
  12. 12.
    Hughes J, Rees S, Kalindjian S, Philpott K (2011) Principles of early drug discovery. Br J Pharmacol 162(6):1239–1249CrossRefGoogle Scholar
  13. 13.
    Neves M, Fausto R (1998) Computational chemistry and metal-based radiopharmaceuticals, (IAEA-TECDOC–1029), International Atomic Energy AgencyGoogle Scholar
  14. 14.
    Chen K, Adelstein SJ, Kassis AI (2004) Molecular modeling of the interaction of iodinated Hoechst analogs with DNA: implications for new radiopharmaceutical design. J Mol Struct (Thoechem) 711:49–56CrossRefGoogle Scholar
  15. 15.
    Al-Wabli RI, Sakr TM, Khedr MA, Selim AA, Motaleb MA, Zaghary WA (2016) Platelet-12 lipoxygenase targeting via a newly synthesized curcumin derivative radiolabeled with technetium-99m. Chem Central J. doi: 10.1186/s13065-016-0220-x Google Scholar
  16. 16.
    Bayoumi NA, Anwer AM, Ismail NS, Abouzid KA, EI-Kolaly MT (2015) Radioiodination and biological evaluation of Cladribine as potential agent for tumor imaging and therapy. Radiochim Acta. 103(11):777–787CrossRefGoogle Scholar
  17. 17.
    Rashed HM, Marzook FA, Farag H (2016) 99mTc-Zolmitriptan: radiolabeling, molecular modeling, biodistribution and gamma scintigraphy as a hopeful radiopharmaceutical for lung nuclear imaging. Radiol Med (Torino) 121(12):935–943CrossRefGoogle Scholar
  18. 18.
    Pinder RM, Brogden RN, Speight TM, Avery GS (1977) Hexoprenaline: a review of its pharmacological properties and therapeutic efficacy with particular reference to asthma. Drugs 14(1):1–28CrossRefGoogle Scholar
  19. 19.
    Woytoń J, Zimmer M, Fuchs T (1999) The use of Gynipral (hexoprenaline) in suppression of uterus contractions. Ginekol Pol 70(12):896–900Google Scholar
  20. 20.
    McMahon CG (2012) Dapoxetine: a new option in the medical management of premature ejaculation. Ther Adv Urol 4(5):233–251CrossRefGoogle Scholar
  21. 21.
    Kendirci M, Salem E, Hellstrom WJG (2007) Dapoxetine, a novel selective serotonin transport inhibitor for the treatment of premature ejaculation. Ther Clin Risk Manag 3(2):277–289CrossRefGoogle Scholar
  22. 22.
    Suhara T, Sudo Y, Yoshida K, Okubo Y, Fukuda H, Obata T, Yoshikawa K, Suzuki K, Sasaki Y (1998) Lung as reservoir for antidepressants in pharmacokinetic drug interactions. Lancet 351:332–335CrossRefGoogle Scholar
  23. 23.
    Motaleb MA, El-Kolaly MT, Rashed HM, Abd El-Bary A (2012) Radioiodinated paroxetine, a novel potential radiopharmaceutical for lung perfusion scan. J Radioanal Nucl Chem 292:629–635CrossRefGoogle Scholar
  24. 24.
    Motaleb MA, El-Kolaly MT, Rashed HM, Abd El-Bary A (2011) Novel radioiodinated sibutramine and fluoxetine as models for brain imaging. J Radioanal Nucl Chem 289:915–921CrossRefGoogle Scholar
  25. 25.
    Rashed HM, Ibrahim IT, Motaleb MA, Abd El-Bary A (2014) Preparation of radioiodinated ritodrine as a potential agent for lung imaging. J Radioanal Nucl Chem 300:1227–1233CrossRefGoogle Scholar
  26. 26.
    Sánchez-Martínez M, Da Costa R, Martins RD, Quincoces G, Gamazo C, Caicedo C, Irache JM, Peñuelas I (2013) Radiolabeling and biodistribution studies of polymeric nanoparticles as adjuvants for ocular vaccination against brucellosis. Rev Esp Med Nucl Imagen Mol. 32:92–97Google Scholar
  27. 27.
    Geskovski N, Kuzmanovska S, Crcarevska MS, Calis S, Dimchevska S, Petrusevska M, Zdravkovski P, Goracinova K (2013) Comparative biodistribution studies of technetium-99 m radiolabeled amphiphilic nanoparticles using three different reducing agents during the labeling procedure. J Label Compd Radiopharm 56(14):689–695CrossRefGoogle Scholar
  28. 28.
    Dorfman KD, King SB, Olson DW, Thomas JP, Tree DR (2013) Beyond gel electrophoresis: microfluidic separations, fluorescence burst analysis, and DNA stretching. Chem Rev 113(4):2584–2667CrossRefGoogle Scholar
  29. 29.
    Konan YN, Cerny R, Favet J, Berton M, Gurny R, Allémann E (2003) Preparation and characterization of sterile sub-200 nm meso-tetra(4-hydroxylphenyl) porphyrin-loaded nanoparticles for photodynamic therapy. Eur J Pharm Biopharm 55(1):115–124CrossRefGoogle Scholar
  30. 30.
    Zhang Y, Lee HJ, Boado RJ, Pardridge WM (2002) Receptor-mediated delivery of an antisense gene to human brain cancer cells. J Gene Med 4(2):183–194CrossRefGoogle Scholar
  31. 31.
    Rashed HM, Shamma RN, Basalious EB (2017) Contribution of both olfactory and systemic pathways for brain targeting of nimodipine-loaded Lipo-pluronics micelles: in vitro characterization and in vivo biodistribution study after intranasal and intravenous delivery. Drug Deliv 24(1):181–187CrossRefGoogle Scholar
  32. 32.
    Nour Samia A, Abdelmalak Nevine S, Naguib Marianne J, Rashed Hassan M, Ibrahim Ahmed B (2016) Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies. Drug Deliv 23(9):3681–3695CrossRefGoogle Scholar
  33. 33.
    Sakr TM, Motaleb MA, Ibrahim IT (2012) 99mTc-meropenem as a potential SPECT imaging probe for tumor hypoxia. J Radioanal Nucl Chem 292(2):705–710CrossRefGoogle Scholar
  34. 34.
    Abd-Elal RM, Shamma RN, Rashed HM et al (2016) Trans-nasal Zolmitriptan Novasomes: in vitro preparation, optimization and invivo evaluation of brain targeting efficiency. Drug Deliv 23(9):3374–3386CrossRefGoogle Scholar
  35. 35.
    Dähnert W (2011) Radiology review manual, 7th edn. Wolters Kluwer, PhiladelphiaGoogle Scholar
  36. 36.
    Lemke TL, Williams DA (2012) Foye’s principles of medicinal chemistry, 7th edn. Lippincott williams & wilkins, BaltimoreGoogle Scholar
  37. 37.
    Fischer J, Ganellin CR (2010) Analogue-based drug discovery II. Wiley-VCH, New YorkCrossRefGoogle Scholar
  38. 38.
    Harden RM, Alexander WD, Kennedy I (1967) Isotope uptake and scanning of stomach in man with 99mTc-pertechnetate. Lancet 289(7503):1305–1307CrossRefGoogle Scholar
  39. 39.
    Kuchar M, Oliveira MC, Gano L, Santos I, Kniess T (2012) Radioiodinated sunitinib as a potential radiotracer for imaging angiogenesis-radiosynthesis and first radiopharmacological evaluation of 5-[125I]Iodo-sunitinib. Bioorg Med Chem Lett 22(8):2850–2855CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2017

Authors and Affiliations

  1. 1.Labeled Compounds Department, Hot Labs. CenterEgyptian Atomic Energy AuthorityCairoEgypt

Personalised recommendations