Springer Protocols: Abstract: Radiometal-Labeled Somatostatin Analogs for Applications in Cancer Imaging and Therapy

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

By: Jason S. Lewis², Carolyn J. Anderson²

Abstract

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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.

Affiliation(s): (2) Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO

Book Title: Peptide Characterization and Application Protocols

Series: Methods in Molecular Biology | Volume: 386 | Pub. Date: May-11-2007 | Page Range: 227-240 | DOI: 10.1007/978-1-59745-430-8_8

Subject: Protein Science

Key Words: Radiometal - peptide - bifunctional chelator - PET - somatostatin - imaging - therapy

References

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

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

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

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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.

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

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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