Advertisement

Journal of Radioanalytical and Nuclear Chemistry

, Volume 302, Issue 1, pp 273–280 | Cite as

PET imaging of sterile inflammation with a 18F-labeled bis(zinc(II)-dipicolylamine) complex

  • Hongliang WangEmail author
  • Ganghua TangEmail author
  • Kongzhen Hu
  • Tingting Huang
  • Xiang Liang
  • Sijin Li
  • Zhifang Wu
Article

Abstract

Small-molecular probe 18F-labeled bis(zinc(II)-dipicolylamine) complex (18F-FB-DPAZn2) was evaluated for PET imaging of sterile inflammation. In comparison with 18F-2-deoxy-β-d-glucose (18F-FDG), 18F-radiolabeled Annexin V (18F-FB-Annexin V) showed rapid clearance of radioactivity from the kidney and low uptake in most tissues. Both the lower radioactivity accumulation in brain and heart and the higher uptakes in the lung, liver, and intestine were observed for the biodistribution of 18F-FB-DPAZn2. In PET imaging, 18F-FDG showed significantly higher tumor and inflammation uptake than did of 18F-FB-DPAZn2 and 18F-FB-Annexin V in the S-180 fibrosarcoma mouse model and sterile inflammation mouse model. Both 18F-FB-DPAZn2 and 18F-FB-Annexin V performed the specifically localization in inflammation, and the ratios of inflammatory lesion-to-muscle and tumor-to-muscle were 1.83 ± 0.20 and 0.90 ± 0.12 (P < 0.05) for 18F-FB-DPAZn2, and 1.51 ± 0.14 and 1.21 ± 0.12 (P > 0.05) for 18F-FB-Annexin V, respectively. Terminal deoxynucleotide end-labeling (TUNEL) assays performed on the dissected tissues showed the significantly more TUNEL-positive nuclei in the inflammatory muscle than in tumor and normal muscle, and these TUNEL results correlated with the uptake of 18F-FB-DPAZn2 in dissected tissues. Biodistribution and PET imaging studies showed that the 18F-FB-DPAZn2 is suitable for imaging sterile inflammation in vivo and is capable of the differentiating tumor from inflammation.

Keywords

Positron emission tomography Sterile inflammation Phosphatidylserine Zinc(II)-dipicolylamine Cell death 

Notes

Acknowledgments

The authors would like to thank Dr. Xiang song Zhang for his useful assistance. This work was supported by the National Natural Science Foundation (No. 81101076, 30970856, 81171374), Postdoctoral Science Foundation of China (20110490964), Science and Technology Planning Project of Guangdong Province, China (2010B031600054 and 2012B031800082) and Hundred Talents Program of Sun Yat-Sen University (No. 18901205).

References

  1. 1.
    Kennedy AD, DeLeo FR (2009) Neutrophil apoptosis and the resolution of infection. Immunol Res 43:25–61CrossRefGoogle Scholar
  2. 2.
    Fialkow L, Fochesatto Filho L, Bozzetti MC, Milani AR, Rodrigues Filho EM, Ladniuk RM, Pierozan P, de Moura RM, Prolla JC, Vachon E, Downey GP (2006) Neutrophil apoptosis: a marker of disease severity in sepsis and sepsis-induced acute respiratory distress syndrome. Crit Care 10:R155CrossRefGoogle Scholar
  3. 3.
    Conus S, Perozzo R, Reinheckel T, Peters C, Scapozza L, Yousefi S, Simon HU (2008) Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation. J Exp Med 205:685–698CrossRefGoogle Scholar
  4. 4.
    Rossi AG, Sawatzky DA, Walker A, Ward C, Sheldrake TA, Riley NA, Caldicott A, Martinez-Losa M, Walker TR, Duffin R, Gray M, Crescenzi E, Martin MC, Brady HJ, Savill JS, Dransfield I, Haslett C (2006) Cyclin-dependent kinase inhibitors enhance the resolution of inflammation by promoting inflammatory cell apoptosis. Nat Med 12:1056–1064CrossRefGoogle Scholar
  5. 5.
    Kettritz R, Gaido ML, Haller H, Luft FC, Jennette CJ, Falk RJ (1998) Interleukin-8 delays spontaneous and tumor necrosis factor-alpha-mediated apoptosis of human neutrophils. Kidney Int 53:84–91CrossRefGoogle Scholar
  6. 6.
    Bratton DL, Fadok VA, Richter DA, Kailey JM, Guthrie LA, Henson PM (1997) Appearance of phosphatidylserine on apoptotic cells requires calcium-mediated nonspecific flip-flop and is enhanced by loss of the aminophospholipid translocase. J Biol Chem 272:26159–26165CrossRefGoogle Scholar
  7. 7.
    Blankenberg FG (2008) In vivo detection of apoptosis. J Nucl Med 49(Suppl 2):81S–95SCrossRefGoogle Scholar
  8. 8.
    Li X, Link JM, Stekhova S, Yagle KJ, Smith C, Krohn KA, Tait JF (2008) Site-specific labeling of annexin V with F-18 for apoptosis imaging. Bioconjug Chem 19:1684–1688CrossRefGoogle Scholar
  9. 9.
    Zhang R, Lu W, Wen X, Huang M, Zhou M, Liang D, Li C (2011) Annexin A5-conjugated polymeric micelles for dual SPECT and optical detection of apoptosis. J Nucl Med 52:958–964CrossRefGoogle Scholar
  10. 10.
    Hanshaw RG, Lakshmi C, Lambert TN, Johnson JR, Smith BD (2005) Fluorescent detection of apoptotic cells by using zinc coordination complexes with a selective affinity for membrane surfaces enriched with phosphatidylserine. ChemBioChem 6:2214–2220CrossRefGoogle Scholar
  11. 11.
    Smith BA, Akers WJ, Leevy WM, Lampkins AJ, Xiao S, Wolter W, Suckow MA, Achilefu S, Smith BD (2010) Optical imaging of mammary and prostate tumors in living animals using a synthetic near infrared zinc(II)-dipicolylamine probe for anionic cell surfaces. J Am Chem Soc 132:67–69CrossRefGoogle Scholar
  12. 12.
    Thakur ML, Zhang K, Paudyal B, Devakumar D, Covarrubias MY, Chen CP, Gray BD, Wickstrom E, Pak KY (2012) Targeting apoptosis for optical imaging of infection. Mol Imaging Biol 14:163–171CrossRefGoogle Scholar
  13. 13.
    White AG, Fu N, Leevy WM, Lee JJ, Blasco MA, Smith BD (2010) Optical imaging of bacterial infection in living mice using deep-red fluorescent squaraine rotaxane probes. Bioconjug Chem 21:1297–1304CrossRefGoogle Scholar
  14. 14.
    Chen K, Yap L, Park R, Gray B, Pak K, Conti P (2011) Evaluation of 64Cu-labeled dipicolylamine (DPA) as a small-molecule PET probe for in vivo imaging of phosphatidylserine exposure. J Nucl Med 52:1502Google Scholar
  15. 15.
    Wyffels L, Gray BD, Barber C, Moore SK, Woolfenden JM, Pak KY, Liu Z (2011) Synthesis and preliminary evaluation of radiolabeled bis(zinc(II)-dipicolylamine) coordination complexes as cell death imaging agents. Bioorg Med Chem 19:3425–3433CrossRefGoogle Scholar
  16. 16.
    Liu X, Cheng D, Gray BD, Wang Y, Akalin A, Rusckowski M, Pak KY, Hnatowich DJ (2012) Radiolabeled Zn-DPA as a potential infection imaging agent. Nucl Med Biol 39:709–714CrossRefGoogle Scholar
  17. 17.
    Wu C, Li F, Niu G, Chen X (2013) PET imaging of inflammation biomarkers. Theranostics 3:448–466CrossRefGoogle Scholar
  18. 18.
    Wang H, Tang X, Tang G, Huang T, Liang X, Hu K, Deng H, Yi C, Shi X, Wu K (2013) Noninvasive positron emission tomography imaging of cell death using a novel small-molecule probe, 18F-labeled bis(zinc(II)-dipicolylamine) complex. Apoptosis 18:1017–1027CrossRefGoogle Scholar
  19. 19.
    Guo XY, Wang HL, Jin YF, Liu YH, Tang G, Jiang SD (2011) Synthesis and radiolabelling of [18F]FEDPA as an imaging agent for apoptosis. J Nuclear Radiochem 33:245–251Google Scholar
  20. 20.
    Grierson JR, Yagle KJ, Eary JF, Tait JF, Gibson DF, Lewellen B, Link JM, Krohn KA (2004) Production of [F-18]fluoroannexin for imaging apoptosis with PET. Bioconjug Chem 15:373–379CrossRefGoogle Scholar
  21. 21.
    Yamada S, Kubota K, Kubota R, Ido T, Tamahashi N (1995) High accumulation of fluorine-18-fluorodeoxyglucose in turpentine-induced inflammatory tissue. J Nucl Med 36:1301–1306Google Scholar
  22. 22.
    Akgul C, Moulding DA, Edwards SW (2001) Molecular control of neutrophil apoptosis. FEBS Lett 487:318–322CrossRefGoogle Scholar
  23. 23.
    Penn DL, Kim C, Zhang K, Mukherjee A, Devakumar D, Jungkind D, Thakur ML (2010) Apoptotic abscess imaging with 99mTc-HYNIC-rh-Annexin-V. Nucl Med Biol 37:29–34CrossRefGoogle Scholar
  24. 24.
    Leevy WM, Gammon ST, Johnson JR, Lampkins AJ, Jiang H, Marquez M, Piwnica-Worms D, Suckow MA, Smith BD (2008) Noninvasive optical imaging of staphylococcus aureus bacterial infection in living mice using a bis-dipicolylamine-Zinc(II) affinity group conjugated to a near-infrared fluorophore. Bioconjug Chem 19:686–692CrossRefGoogle Scholar
  25. 25.
    Murakami Y, Takamatsu H, Taki J, Tatsumi M, Noda A, Ichise R, Tait JF, Nishimura S (2004) 18F-labelled annexin V: a PET tracer for apoptosis imaging. Eur J Nucl Med Mol Imaging 31:469–474CrossRefGoogle Scholar
  26. 26.
    Rayburn ER, Ezell SJ, Zhang R (2009) Anti-inflammatory agents for cancer therapy. Mol Cell Pharmacol 1:29–43CrossRefGoogle Scholar
  27. 27.
    McDonald JU, Cortini A, Rosas M, Fossati-Jimack L, Ling GS, Lewis KJ, Dewitt S, Liddiard K, Brown GD, Jones SA, Hallett MB, Botto M, Taylor PR (2011) In vivo functional analysis and genetic modification of in vitro-derived mouse neutrophils. FASEB J 25:1972–1982CrossRefGoogle Scholar
  28. 28.
    Rusckowski M, Qu T, Pullman J, Marcel R, Ley AC, Ladner RC, Hnatowich DJ (2000) Inflammation and infection imaging with a 99mTc-neutrophil elastase inhibitor in monkeys. J Nucl Med 41:363–374Google Scholar
  29. 29.
    Kubota R, Yamada S, Kubota K, Ishiwata K, Tamahashi N, Ido T (1992) Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography. J Nucl Med 33:1972–1980Google Scholar
  30. 30.
    Strauss LG (1996) Fluorine-18 deoxyglucose and false-positive results: a major problem in the diagnostics of oncological patients. Eur J Nucl Med 23:1409–1415CrossRefGoogle Scholar
  31. 31.
    Liu RS, Chou TK, Chang CH, Wu CY, Chang CW, Chang TJ, Wang SJ, Lin WJ, Wang HE (2009) Biodistribution, pharmacokinetics and PET imaging of [18F]FMISO, [18F]FDG and [18F]FAc in a sarcoma- and inflammation-bearing mouse model. Nucl Med Biol 36:305–312CrossRefGoogle Scholar
  32. 32.
    van Waarde A, Cobben DC, Suurmeijer AJ, Maas B, Vaalburg W, de Vries EF, Jager PL, Hoekstra HJ, Elsinga PH (2004) Selectivity of 18F-FLT and 18F-FDG for differentiating tumor from inflammation in a rodent model. J Nucl Med 45:695–700Google Scholar
  33. 33.
    Deng H, Tang X, Wang H, Tang G, Wen F, Shi X, Yi C, Wu K, Meng Q (2011) S-11C-methyl-l-cysteine: a new amino acid PET tracer for cancer imaging. J Nucl Med 52:287–293CrossRefGoogle Scholar
  34. 34.
    Leevy WM, Gammon ST, Jiang H, Johnson JR, Maxwell DJ, Jackson EN, Marquez M, Piwnica-Worms D, Smith BD (2006) Optical imaging of bacterial infection in living mice using a fluorescent near-infrared molecular probe. J Am Chem Soc 128:16476–16477CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2014

Authors and Affiliations

  1. 1.Department of Nuclear MedicineThe First Affiliated Hospital of Shanxi Medical UniversityTaiyuanChina
  2. 2.Department of Nuclear MedicineThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouChina

Personalised recommendations