Skip to main content

Radiometal-Labeled Somatostatin Analogs for Applications in Cancer Imaging and Therapy

  • Protocol

Part of the Methods in Molecular Biology™ book series (MIMB,volume 386)

Summary

The use of radiolabeled peptides for the diagnosis and therapy of cancer has increased greatly over the last few decades. Skillfully crafted peptide systems, which have high affinity for receptors that are overexpressed in human tumors, offer the potential to improve the characterization, grading, and eventual therapy of human cancer. Robust peptide systems can be labeled with radioactive atoms for imaging purposes using single-photon emission computed tomography and positron emission tomography technologies, or can be labeled with therapeutic nuclides for the efficient killing of tumor cells. This method-based review discusses one such class of receptor-targeted peptides and their radiolabeling with radioactive metals. The somatostatin receptor is upregulated in many types of cancer, and when labeled with a radiometal atom via a bifunctional chelate, can be employed as an agent for the imaging and radiotherapy of cancer. This review will discuss the methods used in the synthesis of the somatostatin peptides, conjugation with bifunctional chelators, and radiolabeling with metal radionuclides. Methods will also be presented for the in vitro and in vivo evaluation of the compounds produced.

Key Words

  • Radiometal
  • peptide
  • bifunctional chelator
  • PET
  • somatostatin
  • imaging
  • therapy

This is a preview of subscription content, access via your institution.

Buying options

Protocol
USD   49.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-59745-430-8_8
  • Chapter length: 14 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   129.00
Price excludes VAT (USA)
  • ISBN: 978-1-59745-430-8
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   169.99
Price excludes VAT (USA)
Hardcover Book
USD   169.99
Price excludes VAT (USA)
Fig. 1
Fig. 2

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Reichlin, S. (1983) Somatostatin (part 1). New Engl. J. Med. 309,1495–1501.

    PubMed  CrossRef  CAS  Google Scholar 

  2. Reichlin, S. (1983) Somatostatin (part 2). New Engl. J. Med. 309,1556–1563.

    PubMed  CrossRef  CAS  Google Scholar 

  3. Guillemin, R. (1978) Peptides in the brain: the new endocrinology of the neuron. Science 202,390–402.

    PubMed  CrossRef  CAS  Google Scholar 

  4. Reubi, J. C., Kvols, L. K., Krenning, E. P., and Lamberts, S. W. J. (1990) Distribution of somatostatin receptors in normal and tumor tissue. Metabolism 39(Suppl 2),78–81.

    PubMed  CrossRef  CAS  Google Scholar 

  5. Bauer, W., Briner, U., Doepfner, W., et al. (1982) SMS 201-995. Life Sci. 31,1133–1140.

    PubMed  CrossRef  CAS  Google Scholar 

  6. de Jong, M., Bernard, B. F., de Bruin, E., et al. (1998) Internalization of radiolabelled [DTPA0]octreotide and [DOTA0, Tyr3]octreotide: peptides for somatostatin receptor-targeted scintigraphy and radionuclide therapy. Nucl. Med. Commun. 19,283–288.

    PubMed  CrossRef  Google Scholar 

  7. de Jong, M., Breeman, W. A. P., Bakker, W. H., et al. (1998) Comparison of 111In-labeled somatostatin analogues for tumor scintigraphy and radionuclide therapy. Cancer Res. 58,437–441.

    PubMed  Google Scholar 

  8. Lewis, J. S., Lewis, M. R., Srinivasan, A., Schmidt, M. A., Wang, J., and Anderson, C. J. (1999) Comparison of four 64Cu-labeled somatostatin analogs in vitro and in a tumor-bearing rat model: Evaluation of new derivatives for PET imaging and targeted radiotherapy. J. Med. Chem. 42,1341–1347.

    PubMed  CrossRef  CAS  Google Scholar 

  9. Krenning, E. P., Bakker, W. H., Kooij, P. P. M., et al. (1992) Somatostatin receptor scintigraphy with indium-111-DTPA-D-Phe-1-octreotide in man: metabolism, dosimetry and comparison with iodine-123-Tyr-3-octreotide. J. Nucl. Med. 33,652–658.

    PubMed  CAS  Google Scholar 

  10. Anderson, C. J., Pajeau, T. S., Edwards, W. B., Sherman, E. L. C., Rogers, B. E., and Welch, M. J. (1995) In vitro and in vivo evaluation of copper-64-labeled octreotide conjugates. J. Nucl. Med. 36,2315–2325.

    PubMed  CAS  Google Scholar 

  11. Anderson, C. J., Jones, L. A., Bass, L. A., et al. (1998) Radiotherapy, toxicity and dosimetry of copper-64-labeled TETA-octreotide in tumor-bearing rats. J. Nucl. Med. 39,1944–1951.

    PubMed  CAS  Google Scholar 

  12. Lewis, J. S., Srinivasan, A., Schmidt, M. A., Schwarz, S. W., Jones, L. A., and Anderson, C. J. (1998) Radiotherapy and dosimetry of copper-64-TETA-Tyr3-octreotate in a somatostatin receptor positive tumor bearing animal model [abstract]. J. Nucl. Med. 39,104P.

    Google Scholar 

  13. Anderson, C. J., Dehdashti, F., Cutler, P. D., et al. (2001) Copper-64-TETA-octreotide as a PET imaging agent for patients with neuroendocrine tumors. J. Nucl. Med. 42,213–221.

    PubMed  CAS  Google Scholar 

  14. Sprague, J. E., Peng, Y., Sun, X., et al. (2004) Preparation and biological evaluation of copper-64–labeled Tyr3-octreotate using a cross-bridged macrocyclic chelator. Clin. Cancer Res. 10,8674–8682.

    PubMed  CrossRef  CAS  Google Scholar 

  15. de Jong, M., Valkema, R., Kwekkeboom, D. J., and Krenning, E. P. (2004) Somatostatin receptor targeted-radio-ablation-of tumors. Endocrine Updates 24,233–249.

    CrossRef  Google Scholar 

  16. Kwekkeboom, D. J., Mueller-Brand, J., Paganelli, G., et al. (2005) Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J. Nucl. Med. 46(suppl. 1),62S–66S.

    PubMed  CAS  Google Scholar 

  17. Maecke, H. R., Hofmann, M., and Haberkorn, U. (2005) 68Ga-labeled peptides in tumor imaging. J. Nucl. Med. 46(suppl. 1),172S–178S.

    PubMed  CAS  Google Scholar 

  18. McQuade, P., Rowland, D. J., Lewis, J. S., and Welch, M. J. (2005) Positron-emitting isotopes produced on biomedical cyclotrons. Curr. Med. Chem. 12,807–818.

    PubMed  CrossRef  CAS  Google Scholar 

  19. Blower, P. J., Lewis, J. S., and Zweit, J. (1996) Copper radionuclides and radiopharmaceuticals in nuclear medicine. Nucl. Med. Biol. 23,957–980.

    PubMed  CrossRef  CAS  Google Scholar 

  20. McCarthy, D. W., Shefer, R. E., Klinkowstein, R. E., et al. (1997) Efficient production of high specific activity 64Cu using a biomedical cyclotron. Nucl. Med. Biol. 24,35–43.

    PubMed  CrossRef  CAS  Google Scholar 

  21. McCarthy, D. W., Bass, L. A., Cutler, P. D., et al. (1999) High purity production and potential applications of copper-60 and copper-61. Nucl. Med. Biol. 26,351–358.

    PubMed  CrossRef  CAS  Google Scholar 

  22. Sun, X., and Anderson, C. J. (2004) Production and applications of copper-64 radiopharmaceuticals. Meth. Enzymol. 386,237–261.

    PubMed  CrossRef  CAS  Google Scholar 

  23. Vavere, A. L., and Welch, M. J. (2005) Preparation, biodistribution, and small animal pet of 45Ti-transferrin. J. Nucl. Med. 46,683–690.

    PubMed  CAS  Google Scholar 

  24. Lewis, M. R., Reichert, D. E., Laforest, R., et al. (2002) Production and purification of gallium-66 for preparation of tumor-targeting radiopharmaceuticals. Nucl. Med. Biol. 29,701–706.

    PubMed  CrossRef  CAS  Google Scholar 

  25. Szelecsenyi, F., Boothe, T. E., Tavano, T., Plitnikas, M. E., and Tarkanyi, F. (1994) Compilation of cross sections/thick target yields for 66Ga, 67Ga and 68Ga production using Zn targets up to 30 MeV proton energy. Appl. Radiat. Isot. 45,473–500.

    CrossRef  CAS  Google Scholar 

  26. Reischl, G., Rosch, F., and Machulla, H. J. (2002) Electrochemical separation and purification of yttrium-86. Radiochim. Acta 90,225–228.

    CrossRef  CAS  Google Scholar 

  27. Roesch, F., and Qaim, S. M. (1993) Nuclear data relevant to the production of the positron emitting technetium isotope 94mTc via the 94Mo(p,n)-reaction. Radiochim. Acta 62,115–121.

    CAS  Google Scholar 

  28. Edwards, W. B., Fields, C. G., Anderson, C. J., Pajeau, T. S., Welch, M. J., and Fields, G. B. (1994) Generally applicable, convenient solid-phase synthesis and receptor affinities of octreotide analogs. J. Med. Chem. 37,3749–3757.

    PubMed  CrossRef  CAS  Google Scholar 

  29. Achilefu, S., Jimenez, H. N., Dorshow, R. B., et al. (2002) Synthesis, in vitro receptor binding and in vivo evaluation of fluorescein and carbocyanine peptide-based optical contrast agents. J. Med. Chem. 45,2003–2015.

    PubMed  CrossRef  CAS  Google Scholar 

  30. Li, W. P., Lewis, J. S., Kim, J., et al. (2002) DOTA-D-Tyr1-octreotate: a somatostatin analog for labeling with halogen and metal radionuclides for cancer imaging and therapy. Bioconjug. Chem. 13,721–728.

    PubMed  CrossRef  CAS  Google Scholar 

  31. Mishra, A. K., Draillard, K., Faivrechauvet, A., Gestin, J. F., Curtet, C., and Chatal, J. F. (1996) A convenient, novel approach for the synthesis of polyaza macrocyclic bifunctional chelating agents. Tetrahedron Lett. 37,7515–7518.

    CrossRef  CAS  Google Scholar 

  32. Yorke, E. D., Williams, L. E., Demidecki, A. J., Heidorn, D. B., Roberson, P. L., and Wessels, B. W. (1993) Multicellular dosimetry for beta-emitting radionuclides: autoradiography, thermoluminescent dosimetry and three-dimensional dose calculations. [review]. Med. Phys. 20,543–550.

    PubMed  CrossRef  CAS  Google Scholar 

  33. Lewis, J. S., Laforest, R., Lewis, M. R., and Anderson, C. J. (2000) Comparative dosimetry of copper-64 and yttrium-90-labeled somatostatin analogs in a tumor-bearing rat model. Cancer Biothet. Radiopharm. 15,593–604.

    CrossRef  CAS  Google Scholar 

  34. Breeman, W. A. P., de Jong, M., Visser, T. J., Erion, J. L., and Krenning, E. P. (2003) Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities. Eur. J. Nucl. Med. Mol. Imag. 30,917–920.

    CrossRef  CAS  Google Scholar 

  35. Breeman, W. A. P., de Jong, M., de Blois, E., Bernard, B. F., Konijnenberg, M., and Krenning, E. P. (2005) Radiolabelling DOTA-peptides with 68Ga. Eur. J. Nucl. Med. Mol. Imag. 32,478–485.

    CrossRef  CAS  Google Scholar 

  36. Longnecker, D. S., Lilja, H. S., French, J., Kuhlmann, E., and Noll, W. (1979) Transplantation of azaserine-induced carcinomas of pancreas in rats. Cancer Lett. 7,197–202.

    PubMed  CrossRef  CAS  Google Scholar 

  37. Rosewicz, S., Vogt, D., Harth, N., et al. (1992) An amphicrine pancreatic cell line: AR42J cells combine exocrine and neuroendocrine properties. Eur. J. Cell Biol. 59,80–91.

    PubMed  CAS  Google Scholar 

  38. Christophe, J. (1994) Pancreatic tumoral cell line AR42J: An amphicrine model. Am. J. Physiol. 266(6 pt 1),G963–G971.

    PubMed  CAS  Google Scholar 

  39. Wipke, B. T., Wang, Z., Kim, J., McCarthy, T. J., and Allen, P. M. (2002) Dynamic visualization of a joint-specific autoimmune response through positron emission tomography. Nat. Immunol. 3,366–372.

    PubMed  CrossRef  CAS  Google Scholar 

  40. Cherry, S. R., Shao, Y., Silverman, R. E., et al. (1997) Micropet: a high resolution pet scanner for imaging small animals. IEEE. Trans. Nucl. Sci. 44,1161–1166.

    CrossRef  CAS  Google Scholar 

  41. Lewis, J. S., Achilefu, S., Garbow, J. R., Laforest, R., and Welch, M. J. (2002) Small animal imaging: current technology and perspectives for oncological imaging. Eur. J. Cancer 38,2173–2188.

    PubMed  CrossRef  Google Scholar 

  42. Rowland, D. J., Lewis, J. S., and Welch, M. J. (2002) Molecular imaging: the application of small animal positron emission tomography. J. Cell. Biochem. Suppl 39,110–115.

    CrossRef  Google Scholar 

  43. Knoess, C., Siegel, S., Smith, A., et al. (2003) Performance evaluation of the microPET R4 pet scanner for rodents. Eur. J. Nucl. Med. Mol. Imag. 30,737–747.

    CrossRef  Google Scholar 

  44. Tai, Y. C., Ruangma, A., Rowland, D. J., et al. (2005) Performance evaluation of the microPET FOCUS: a third-generation microPET scanner dedicated to animal imaging. J. Nucl. Med. 46,455–463.

    PubMed  Google Scholar 

  45. Boswell, C. A., Sun, X., Niu, W., et al. (2004) Comparative in vivo stability of copper-64-labeled cross-bridged and conventional tetraazamacrocyclic complexes. J. Med. Chem. 47,1465–1474.

    PubMed  CrossRef  CAS  Google Scholar 

  46. Sun, X., Wuest, M., Weisman, G. R., et al. (2002) Radiolabeling and in vivo behavior of copper-64-labeled cross-bridged cyclam ligands. J. Med. Chem. 45,469–477.

    PubMed  CrossRef  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2007 Humana Press Inc.

About this protocol

Cite this protocol

Lewis, J.S., Anderson, C.J. (2007). Radiometal-Labeled Somatostatin Analogs for Applications in Cancer Imaging and Therapy. In: Fields, G.B. (eds) Peptide Characterization and Application Protocols. Methods in Molecular Biology™, vol 386. Humana Press. https://doi.org/10.1007/978-1-59745-430-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-430-8_8

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-550-7

  • Online ISBN: 978-1-59745-430-8

  • eBook Packages: Springer Protocols