Annals of Nuclear Medicine

, Volume 27, Issue 10, pp 892–897 | Cite as

Novel Tc-99m labeled ELR-containing 6-mer peptides for tumor imaging in epidermoid carcinoma xenografts model: a pilot study

  • Dae-Weung Kim
  • Woo Hyoung Kim
  • Myoung Hyoun Kim
  • Chang Guhn KimEmail author
Original Article



ELR-containing peptides targeting CXCR2 could be the excellent candidate for targeting ligand of molecular tumor imaging. In this study, we had developed two ELR-containing 6-mer peptides and evaluated the diagnostic performance of Tc-99m labeled 6-mer peptides as a molecular imaging agent in murine models bearing KB epidermoid carcinoma.


Peptides were synthesized using Fmoc solid phase peptide synthesis. Radiolabeling efficiency with Tc-99m was evaluated using instant thin-layer chromatography. In KB epidermoid cancer-bearing mice, gamma images had acquired and tumor-to-muscle uptake ratio was calculated. Competition and biodistribution studies had performed.


Two 6-mer peptides, ELR-ECG and ECG-ELR were successfully synthesized. After radiolabeling procedures with Tc-99m, the complex Tc-99m ELR-ECG and Tc-99m ECG-ELR were prepared in high yield. In the gamma camera imaging of murine model, Tc-99m ELR-ECG was substantially accumulated in the subcutaneously engrafted tumor and tumor uptake had been suppressed by the free ELR co-injection. However, Tc-99m ECG-ELR was minimally accumulated in the tumor.


Two ELR-containing 6-mer peptides, ELR-ECG and ECG-ELR, were developed as a molecular imaging agent to target CXCR2 of epidermoid carcinoma. Tc-99m ELR-ECG had showed significant uptake in tumor and it was good candidate for a tumor imaging.


CXC chemokine Glutamic acid-leucine-arginine ELR CXCR2 Tc-99m 



This paper was supported by Wonkwang Institute of Clinical Medicine in 2012.


  1. 1.
    Strieter RM, Burdick MD, Mestas J, Gomperts B, Keane MP, Belperio JA. Cancer CXC chemokine networks and tumour angiogenesis. Eur J Cancer. 2006;42:768–78.PubMedCrossRefGoogle Scholar
  2. 2.
    Luster AD. Chemokines—chemotactic cytokines that mediate inflammation. N Engl J Med. 1998;338:436–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Belperio JA, Keane MP, Arenberg DA, Addison CL, Ehlert JE, Burdick MD, et al. CXC chemokines in angiogenesis. J Leukoc Biol. 2000;68:1–8.PubMedGoogle Scholar
  4. 4.
    Addison CL, Daniel TO, Burdick MD, Liu H, Ehlert JE, Xue YY, et al. The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR + CXC chemokine-induced angiogenic activity. J Immunol. 2000;165:5269–77.PubMedGoogle Scholar
  5. 5.
    Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.PubMedCrossRefGoogle Scholar
  6. 6.
    Waugh DJ, Wilson C. The interleukin-8 pathway in cancer. Clin Cancer Res. 2008;14:6735–41.PubMedCrossRefGoogle Scholar
  7. 7.
    Nannuru KC, Sharma B, Varney ML, Singh RK. Role of chemokine receptor CXCR2 expression in mammary tumor growth, angiogenesis and metastasis. J Carcinog. 2011;10:40.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Venkatakrishnan G, Salgia R, Groopman JE. Chemokine receptors CXCR-1/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells. J Biol Chem. 2000;275:6868–75.PubMedCrossRefGoogle Scholar
  9. 9.
    Wong E, Fauconnier T, Bennett S, Valliant J, Nguyen T, Lau F, et al. Rhenium(V) and Technetium(V) oxo complexes of an N(2)N’S peptidic chelator: evidence of interconversion between the Syn and Anti conformations. Inorg Chem. 1997;36:5799–808.PubMedCrossRefGoogle Scholar
  10. 10.
    Liu S, Edwards DS. 99mTc-labeled small peptides as diagnostic radiopharmaceuticals. Chem Rev. 1999;99:2235–68.PubMedCrossRefGoogle Scholar
  11. 11.
    Rajagopalan L, Rajarathnam K. Ligand selectivity and affinity of chemokine receptor CXCR1. Role of N-terminal domain. J Biol Chem. 2004;279:30000–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Zhu A, Shim H. Current molecular imaging positron emitting radiotracers in oncology. Nucl Med Mol Imaging. 2011;45:1–14.CrossRefGoogle Scholar
  13. 13.
    Kim DW, Kim CG. Effects of DNA ploidy and S-phase fraction on fluorine-18 FDG uptake of primary breast cancer lesions. Clin Breast Cancer. 2013;13:196–201.PubMedCrossRefGoogle Scholar
  14. 14.
    Berger M, Gould MK, Barnett PG. The cost of positron emission tomography in six United States Veterans Affairs hospitals and two academic medical centers. AJR Am J Roentgenol. 2003;181:359–65.PubMedCrossRefGoogle Scholar
  15. 15.
    Yang DJ, Kim EE, Inoue T. Targeted molecular imaging in oncology. Ann Nucl Med. 2006;20:1–11.PubMedCrossRefGoogle Scholar
  16. 16.
    Curnis F, Cattaneo A, Longhi R, Sacchi A, Gasparri AM, Pastorino F, et al. Critical role of flanking residues in NGR-to-isoDGR transition and CD13/integrin receptor switching. J Biol Chem. 2010;285:9114–23.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Society of Nuclear Medicine 2013

Authors and Affiliations

  • Dae-Weung Kim
    • 1
    • 2
    • 3
  • Woo Hyoung Kim
    • 1
    • 2
  • Myoung Hyoun Kim
    • 1
    • 2
  • Chang Guhn Kim
    • 1
    • 2
    Email author
  1. 1.Department of Nuclear MedicineWonkwang University School of MedicineIksanRepublic of Korea
  2. 2.Institute of Wonkwang Medical ScienceWonkwang University School of MedicineIksanKorea
  3. 3.Research Unit of Molecular Imaging Agent (RUMIA)Wonkwang University School of MedicineIksanKorea

Personalised recommendations