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Radiosynthesis and biodistribution studies of [62Zn/62Cu]–plerixafor complex as a novel in vivo PET generator for chemokine receptor imaging

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Abstract

In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [62Zn]labeled 1,1′-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane ([62Zn]-AMD3100) was prepared using in-house made [62Zn]ZnCl2 and AMD-3100 for 1 h at 50 °C (radiochemical purity: >97 % ITLC, >96 % HPLC, specific activity: 20–22 GBq/mmol) in acetate buffer. The complex showed highly hydrophilic properties (log P = −1.114). Stability of the complex was checked in presence of human serum (37 °C) and in final formulation for 1 day. The biodistribution of the labeled compound in vital organs of wild-type Sprague–Dawdley rats were determined and compared with that of free Zn2+ cation up to 6 h. Co-incidence imaging of the complex was consistent with the distribution data up to 3 h. The complex can be a possible in vivo generator compound for PET imaging in CXCR4 positive tumors.

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References

  1. Balkwill F (2004) Cancer and the chemokine network. Nat Rev Cancer 4:540–550

    Article  CAS  Google Scholar 

  2. Masuda M, Nakashima H, Ueda T, Naba H, Ikoma R, Otaka A, Terakawa Y, Tamamura H, Ibuka T, Murakami T, Koyanagi Y, Waki M, Matsumoto A, Yamamoto N, Funakoshi S, Fujii N (1992) A novel anti-HIV synthetic peptide, T-22 ([Tyr5,12, Lys7]-polyphemusin II). Biochem Biophys Res Commun 189:845–850

    Article  CAS  Google Scholar 

  3. Liang Z, Yoon Y, Votaw J, Goodman MM, Williams L, Shim H (2005) Silencing of CXCR4 blocks breast cancer metastasis. Cancer Res 65:967–971

    CAS  Google Scholar 

  4. Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, Luker GD (2004) CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res 64:8604–8612

    Article  CAS  Google Scholar 

  5. Gerlach LO, Jakobsen JS, Jensen KP, Rosenkilde MR, Skerlj RT, Ryde U, Bridger GJ, Schwartz TW (2003) Metal ion enhanced binding of AMD3100 to Asp262 in the CXCR4 receptor. Biochemistry 42:710–717

    Article  CAS  Google Scholar 

  6. Knight JC, Hallett AJ, Brancale A, Paisey SJ, Clarkson RWE, Edwards PG (2011) Evaluation of a fluorescent derivative of AMD3100 and its interaction with the CXCR4 chemokine receptor. Chem Bio Chem 12:2692–2698

    Article  CAS  Google Scholar 

  7. Zhang JM, Tiana JH, Lia TR, Guo HY, Shen L (2010) 99mTc-AMD3100: a novel potential receptor-targeting radiopharmaceutical for tumor imaging. Chin Chem Lett 21:461–463

    Article  CAS  Google Scholar 

  8. Jacobson D, Weiss ID, Szajek L, Farber J, Kiesewetter DO (2009) 64Cu-AMD3100—a novel imaging agent for targeting chemokine receptor CXCR4. Bioorg Med Chem 17:1486–1493

    Article  CAS  Google Scholar 

  9. Nimmagadda S, Pullambhatla M, Stone K, Green G, Bhujwalla ZM, Pomper MG, Morgan RH (2010) Molecular imaging of CXCR4 receptor expression in human cancer xenografts with [64Cu]AMD3100-positron emission tomography. Cancer Res 70:3935–3944

    Article  CAS  Google Scholar 

  10. Jalilian AR, Fateh B, Ghergherehchi M, Karimian A (2005) Development of [62Zn]bleomycin as a possible PET tracer. Nukleonika 50:143–148

    CAS  Google Scholar 

  11. Fujibayashi Y, Saji H, Yomoda I, Kawai K, Horiuchi K, Adachi H, Torizuka K, Yokoyama A (1986) 62Zn-EDDA: a radiopharmaceutical for pancreatic functional diagnosis. Int J Nucl Med Biol 12:439–446

    Article  CAS  Google Scholar 

  12. Ziegler JF, Biersack JP, Littmark U (2000) The stopping and range of ions in matter. SRIM Code, Version 2000 XX

  13. Weisberg AM (1990) Gold plating, 9th edn. ASM International, Metals Park, p 247

  14. Green MA, Mathias CJ, Welch MJ, McGuire AH, Perry D, Fernandez-Rubio F, Perlmutter JS, Raichle ME, Bergmann RB (1990) Copper-62-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II): synthesis and evaluation as a positron emission tomography tracer for cerebral and myocardial perfusion. J Nucl Med 31:1989–1996

    CAS  Google Scholar 

  15. Bormans G, Janssen A, Adriaens P, Crombez D, Witsenboer A, DE Goeij J, Mortelmans L, Verbruggen A (1992) A 62Zn/62Cu generator for the routine production of 62Cu-PTSM. Appl Radiat Isot 43:1437–1441

    Article  CAS  Google Scholar 

  16. Green MA, Klippenstein DL, Tennison JR (1988) Copper(II) bis(thiosemicarbazone) complexes as potential tracers for evaluation of cerebral and myocardial blood flow with PET. J Nucl Med 29:1549–1557

    CAS  Google Scholar 

  17. Jalilian AR, Rowshanfarzad P, Sabet M, Novinrooz A, Raisali G (2005) Preparation of [66Ga]bleomycin complex as a possible PET radiopharmaceutical. J Radioanal Nucl Chem 264:617–622

    Article  CAS  Google Scholar 

  18. Asano T, Asano Y, Iguchi Y, Kudo H, Mori S, Noguchi M, Tahaka Y, Hirabayashi H, Ikeda H, Katoh K, Kondo K, Takasaki M, Tominaka T, Yamamoto A (1983) (p, xn),(p, pxn) and (p,2pxn) reactions medium-mass nuclei at 12 GeV. J Phys Rev Part C Nucl Phys 28:1840

    Article  CAS  Google Scholar 

  19. Ghoshal SN (1950) An experimental verification of the theory of compound nucleus. J Phys Rev 80:939

    Article  CAS  Google Scholar 

  20. Greene MW, Lebowitz E (1972) Proton reactions with copper for auxiliary cyclotron beam monitoring. Int J Appl Radiat Isot 23:342–344

    Article  CAS  Google Scholar 

  21. Grütter A (1982) Excitation functions for radioactive isotopes produced by proton bombardment of Cu and Al in the energy range of 16 to 70 MeV. J Nucl Phys Sect A 383:98–108

    Article  Google Scholar 

  22. Kopecký P (1985) Proton beam monitoring via the Cu(p, x)58Co, 63Cu(p,2n)62Zn and 65Cu(p, n)65Zn reactions in copper. Int J Appl Radiat Isot 36:657–661

    Article  Google Scholar 

  23. Levkovskij VN (1991) Activation cross section nuclides of average masses (A = 40–100) by protons and alpha-particles with average energies (E = 10–50 Mev) by protons and alphas, Moscow. Data downloaded via the internet from the IAEA nuclear data section (experimental nuclear reaction data, http://www.nndc.bnl.gov/Exfor)

  24. Meadows JW (1953) Excitation functions for proton-induced reactions with copper. J Phys Rev 91:885–887

    Article  CAS  Google Scholar 

  25. Mills SJ, Steyn GF, Nortier FM (1992) Experimental and theoretical excitation functions of radionuclides produced in proton bombardment of copper up to 200 MeV. Int J Appl Radiat Isot 43:1019–1030

    Article  CAS  Google Scholar 

  26. Blann M (1975) University of Rochester Report C00-3494-29

  27. Ziegler JF, Biersack JP, Littmark U (1985) The stopping and range of ions in solids, vol 1 of the stopping and ranges of ions in matter. Pergamon Press, Elmsford

  28. Robinson GD Jr, Zielinski FW, Lee AW (1980) The Zn-62/Copper-62 generator: a convenient source of copper-62 for radiopharmaceuticals. Int J Appl Radiat Isot 31:111–116

    Article  CAS  Google Scholar 

  29. United States Pharmacopoeia 28, 2005, NF 23, p 1009

  30. Woodard LE, Nimmagadda S (2011) CXCR4-based imaging agents. J Nucl Med 52:1665–1669

    Article  CAS  Google Scholar 

  31. Nimmagadda S, Pullambhatla M, Pomper MG (2009) Immunoimaging of CXCR4 expression in brain tumor xenografts using SPECT/CT. J Nucl Med 50:1124–1130

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This study has been funded and supported by Tehran University of Medical Sciences, Tehran, Iran; Grant No. 18308. Authors wish to thank Ms. Moradkhani for performing animal tests and Ms. Bolourinovin for instrumental support.

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Authors and Affiliations

  1. Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Ayuob Aghanejad & Davood Beiki

  2. Nuclear Science and Technology Research Institute, Tehran, 11365-3486, Iran

    Amir R. Jalilian & Yousef Fazaeli

  3. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Ayuob Aghanejad

  4. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Ali Khalaj

  5. Faculty of Engineering and Industrial Sciences (H38), Swinburne University of Technology, PO Box 218, Hawthorn, Victoria, 3122, Australia

    Behrooz Fateh

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  1. Ayuob Aghanejad
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  2. Amir R. Jalilian
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  3. Yousef Fazaeli
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  4. Davood Beiki
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  5. Behrooz Fateh
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Correspondence to Amir R. Jalilian.

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Aghanejad, A., Jalilian, A.R., Fazaeli, Y. et al. Radiosynthesis and biodistribution studies of [62Zn/62Cu]–plerixafor complex as a novel in vivo PET generator for chemokine receptor imaging. J Radioanal Nucl Chem 299, 1635–1644 (2014). https://doi.org/10.1007/s10967-013-2822-2

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  • DOI: https://doi.org/10.1007/s10967-013-2822-2

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