Purification and biological evaluation of radioiodinated clozapine as possible brain imaging agent

  • A. M. Amin
  • S. A. Kandil
  • M. E. Abdel-Hameed
  • M. E. Aboselim
  • H. A. El-Ghamry


A method for the preparation of high radiochemical yield 125I-clozapine was developed in order to characterize the binding properties of serotonergic and dopaminergic receptors. This labeling reaction was done by electrophilic substitution giving two radioiodinated products. The major radiolabeled product with a yield reached 91.4 %, and the minor one with a yield 8 %. Different chromatographic techniques (electrophoresis and HPLC) were used to evaluate the radiochemical yield and purity of the labeled products. Biodistribution results indicate that the radioiodo-clozapine cross the blood brain barrier with maximum uptake (10.5 ± 0.4 % injected dose/g tissue at 60 min) and high retention (4.0 ± 0.2 % injected dose/g tissue at 120 min). Brain uptake and retention of 125I-clozapine is higher than that of currently used radiopharmaceuticals for brain imaging.


Radioiodine Clozapine Serotonergic receptors Brain imaging agent 


  1. 1.
    Saha GB, MacIntyre WJ, Go RT (1994) Semin Nucl Med 24(4):324–349CrossRefGoogle Scholar
  2. 2.
    Shenton ME, Turetsky BI (2010) Understanding neuropsychiatric disorders: insights from neuroimaging. Cambridge University Press, Cambridge, p 230CrossRefGoogle Scholar
  3. 3.
    Kung HF, Alavi A, Chang W, Kung MP, Keyes JW, Velchik MG, Billings J, Pan S, Noto R (1990) J Nucl Med 31(5):573–579Google Scholar
  4. 4.
    Ahn K, Gil R, Seibyl J, Sewell RA, D’Souza DC (2011) Neuropsychopharmacology (Nature Publishing Group) 36(3):677–683Google Scholar
  5. 5.
    Kuki I, Kawawaki H, Okazaki S, Inoue T, Nukui M, Tomiwa K, Amou K, Togawa M, Shiomi M (2012) No To Hattatsu 44(1):5–12Google Scholar
  6. 6.
    Diksic M, Reba RC (1991) Radiopharmaceuticals and brain pathophysiology studied with PET and SPECT, vol 33431. CRC Press, Boca Raton, pp 41–69Google Scholar
  7. 7.
    Heiss WD, Herholz K (2006) J Nucl Med 47:302–312Google Scholar
  8. 8.
    Newman-Tancredi A, Kleven MS (2011) Psychopharmacology 216(4):451–473CrossRefGoogle Scholar
  9. 9.
    Meltzer HY, Bastani B, Ramirez L, Matsubara S (1989) Eur Arch Psychiatry Neurol Sci 238(5–6):332–339 ReviewCrossRefGoogle Scholar
  10. 10.
    Fijal K, Popik P, Nikiforuk A (2014) Psychopharmacology 231(1):269–281CrossRefGoogle Scholar
  11. 11.
    Ramírez MJ (2013) Alzheimers Res Ther 5(2):15Google Scholar
  12. 12.
    Korde A, Venkatesh M, Sarma HD (1998) Int. Symposium on modern trends in radiopharmaceuticals for diagnosis and therapy, Lisbon, Portugal, IAEA, SM- 55/13: 43Google Scholar
  13. 13.
    Lam S, Boselli L (1986) Biomed Chromatogr 1(4):177–179CrossRefGoogle Scholar
  14. 14.
    Liu FEI, Youfeng HE, Luo Z (2004) Technical Reports Series No. 426, 37–52, IAEA, AustriaGoogle Scholar
  15. 15.
    Rhodes BA (1974) Semin Nucl Med 4:281CrossRefGoogle Scholar
  16. 16.
    Koehler L, Gagnon K, Mc Quarrie S, Wuest F (2010) Chem Mol 15:2686–2718Google Scholar
  17. 17.
    Sinn HJ, Schrenk HH, Friedrich EA, Via DP, Dresel HA (1988) Anal Biochem 170:186–192CrossRefGoogle Scholar
  18. 18.
    Saccavini JC, Bruneau C (1984) IAEA CN 4519:153Google Scholar
  19. 19.
    Pucci V, Raggi M, Kenndler E (1999) Chromatogr B J 728:263–271CrossRefGoogle Scholar
  20. 20.
    Kaur H, Bassi P, Monif T, Khuroo A, Kaur G (2013) Pak J Pharm Sci 26(3):465–472Google Scholar
  21. 21.
    Verbruggen RF (1986) Int J Appl Radiat Isot 37:1249CrossRefGoogle Scholar
  22. 22.
    Wenthur CJ, Lindsley CW (2013) ACS Chem Neurosci 4(7):1018–1025CrossRefGoogle Scholar
  23. 23.
    Arano Yasushi (2002) Rev Ann Nucl Med 16(2):79–93CrossRefGoogle Scholar
  24. 24.
    Motaleb MA, El-Kolaly MT, Rashed HM, El-Bary AA (2011) J Radioanal Nucl Chem 289(3):915–921CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2015

Authors and Affiliations

  • A. M. Amin
    • 1
  • S. A. Kandil
    • 2
  • M. E. Abdel-Hameed
    • 2
  • M. E. Aboselim
    • 3
  • H. A. El-Ghamry
    • 3
  1. 1.Labeled Compounds Department, Hot Labs CenterAtomic Energy AuthorityCairoEgypt
  2. 2.Cyclotron Project, Nuclear Research CenterAtomic Energy AuthorityCairoEgypt
  3. 3.Faculty of PharmacyZagazig UniversityZagazigEgypt

Personalised recommendations