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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo

Author(s): Ahmet M. Şenışık*, Çiğdem İçhedef, Ayfer Y. Kılçar, Eser Uçar, Kadir Arı, Yasemin Parlak, Elvan S. Bilgin and Serap Teksöz*

Volume 19, Issue 11, 2019

Page: [1382 - 1387] Pages: 6

DOI: 10.2174/1871520619666190404154723

Price: $65

Abstract

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly).

Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging.

Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal.

Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

Keywords: Technetium tricarbonyl core, radiolabeling, glycylglycine, in vivo, SPECT imaging, biodistribution studies.

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[1]
Fani, M.; Maecke, H.R.; Okarvi, S.M. Radiolabeled peptides: Valuable tools for the detection and treatment of cancer. Theranostics, 2012, 2(5), 481-501.
[2]
de Barros, A.L.B.; Cardoso, V.N.; Mota, L. das G.; Leite, E.A.; de Oliveira, M.C.; Alves, R.J. A novel d-glucose derivative radiolabeled with technetium-99m: Synthesis, biodistribution studies and scintigraphic images in an experimental model of Ehrlich tumor. Bioorg. Med. Chem. Lett., 2010, 20, 2478-2480.
[3]
Kharisov, B.I.; Mendez-Rojas, M.A. State-of-the-art coordination chemistry of radioactive elements. Russ. Chem. Rev., 2001, 70, 865-884.
[4]
Dewanjee, M.K. The chemistry of 99mTc-labeled radio-pharmaceuticals. Semin. Nucl. Med., 1990, 20, 5-27.
[5]
Weiner, R.E.; Thakur, M.L. Radiolabeled peptides in the diagnosis and therapy of oncological diseases. Appl. Radiat. Isot., 2002, 57, 749-763.
[6]
Hultsch, C.; Berndt, M.; Bergmann, R.; Wuest, F. Radiolabeling of multimeric neurotensin(8-13) analogs with the short-lived positron emitter fluorine-18. Appl. Radiat. Isot., 2007, 65, 818-826.
[7]
Liu, S.; Edwards, D.S. 99mTc-Labeled small peptides as diagnostic radiopharmaceuticals. Chem. Rev., 1999, 99, 2235-2268.
[8]
Chen, K.; Conti, P.S. Target-specific delivery of peptide-based probes for PET imaging. Adv. Drug Deliv. Rev., 2010, 62, 1005-1022.
[9]
Alberto, R.; Schibli, R.; Schubiger, A.P.; Di, V.; Abram, U.; Dresden, D.; Kaden, T.A. A novel organometallic aqua complex of technetium for the labeling of biomolecules: Aqueous solution and its reaction with a bifunctional ligand. J. Am. Chem. Soc., 1998, 120, 7987-7988.
[10]
Schibli, R.; Schubiger, A.P. Current use and future potential of organometallic radiopharmaceuticals. J. Nucl. Med., 2002, 29, 1529-1542.
[11]
Schibli, R.; La Bella, R.; Alberto, R.; Garcia-Garayoa, E.; Ortner, K.; Abram, U.; Schubiger, P.A. Influence of the denticity of ligand systems on the in vitro and in vivo behavior of 99mTc(I)-tricarbonyl complexes: A hint for the future functionalization of biomolecules. Bioconjug. Chem., 2000, 11, 345-351.
[12]
Morais, G.R.; Paulo, A.; Santos, I. Organometallic complexes for SPECT imaging and/or radionuclide therapy. Organometallics, 2012, 31, 5693-5714.
[13]
García-Garayoa, E.; Bläuenstein, P.; Bruehlmeier, M.; Blanc, A.; Iterbeke, K.; Conrath, P.; Tourwé, D.; Schubiger, P.A. Preclinical evaluation of a new, stabilized neurotensin(8-13) pseudopeptide radiolabeled with 99mTc. J. Nucl. Med., 2002, 43, 374-383.
[14]
Şenışık, A.M.; İçhedef, Ç.; Kılçar, A.Y.; Uçar, E.; Arı, K.; Göksoy, D.; Parlak, Y.; Bilgin, S.B.E.; Teksöz, S. One-step conjugation of glycylglycine with [18F]FDG and a pilot PET imaging study. J. Radioanal. Nucl. Chem., 2018, 316, 457-463.
[15]
Jang, B.S.; Lee, J.S.; Rho, J.K.; Park, S.H. Biodistribution of99mTc tricarbonyl glycine oligomers. Toxicol. Res., 2012, 28, 235-240.
[16]
Alves, S.; Paulo, A.; Correia, J.D.G.; Gano, L.; Smith, C.J.; Hoffman, T.J.; Santos, I. Pyrazolyl derivatives as bifunctional chelators for labeling tumor-seeking peptides with the fac-[M(CO)3]+ moiety (M = 99mTc, Re): Synthesis, characterization, and biological behavior. Bioconjug. Chem., 2005, 16, 438-449.
[17]
Jang, B.S.; Kim, Y.M.; Choi, S.M.; Shin, B.C.; Choi, S.J.; Hong, Y.D.; Gwon, H.J.; Park, K.B. Synthesis of 99mTc-tricarbonyl precursors for labeling of bioactive molecules. J. Korean Nucl. Soc, 2002, 34, 146-153.
[18]
Tsiapa, I.; Loudos, G.; Varvarigou, A.; Fragogeorgi, E.; Psimadas, D.; Tsotakos, T.; Xanthopoulos, S.; Mihailidis, D.; Bouziotis, P.; Nikiforidis, G.C.; Kagadis, G.C. Biological evaluation of an ornithine-modified 99mTc-labeled RGD peptide as an angiogenesis imaging agent. Nucl. Med. Biol., 2013, 40, 262-272.

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