Use of non-aqueous solvents in the synthesis of radioconjugate DOTA-1--octreotide labeled with gallium-68
Main Article Content
Abstract
Neuroendocrine tumors specifically over-express somatostatin receptors. Their diagnosis has expanded due to radiolabelling of DOTA-peptides such as somatostatin analogue DOTA-1--Octreotide (DOTA-NOC) conjugated to ?+ emitting radionuclides such as , with very favorable decay-properties. This paper describes the radiolabeling procedures of DOTA-NOC with , in a pure aqueous medium and in presence of non-aqueous solvents as well as the methods used for quality control where a formulation is obtained with a radiochemical yield exceeding 95%. Adding ethanol (30 % - v / v) to the reaction mixture allowed increasing the specific activity of -DOTA-NOC radioconjugated, reaching a value of 182 MBq / nmol, higher than reported in literature (50 MBq / nmol) for labeling in a pure aqueous medium. Stability studies are also presented (in presence of saline solution and saline phosphate buffer, transmetallation studies in , , and solutions, challenges competition against EDTA and DTPA chelators and in vitro stability in human transferrin) performed to -DOTA-NOC radioconjugated, showing its high stability (> 95 %). Compared with the aqueous medium, the use of non aqueous solvents in the synthesis of radioconjugate DOTA-1--octreotide labeled with gallium-68, helps reduce the mass of conjugate and the reaction time, significantly increase yields and specific activity of the labeled compound. This could facilitate obtaining the product with better characteristics in modular systems that are under development.
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How to Cite
Pérez-Malo Cruz, M., & Leyva Montaña, R. (1). Use of non-aqueous solvents in the synthesis of radioconjugate DOTA-1--octreotide labeled with gallium-68. Nucleus, (59). Retrieved from http://nucleus.cubaenergia.cu/index.php/nucleus/article/view/618
Section
Ciencias Nucleares
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References
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[13] ANTUNES P, GINJ M, ZHANG H, et. al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?. Eur.J. Nucl. Med. Mol. Imaging. 2007; 34(7): 982-993.
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[16] MOERLEIN SM, WELCH MJ. The chemistry of gallium and indium as related to radiopharmaceutical production. Int. J. Nucl. Med. Biol. 1981; 8(4): 277-287.
[17] ZHANG Z. Bioinorganic chemistry of Aluminum, Gallium, and Indium complexes of 1-aryl-3-oxy-4-pyridinones [tesis on line] [doctoral thesis in philosophy]. University of British Columbia, december 1991. https://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0061723.
[2] FANI M, DEL POZZO L, ABIRAJ K, et. al. PET of somatostatin receptor–positive tumors using 64Cu- and 68Ga-somatostatin antagonists: the chelate makes the difference. J Nucl Med. 2011; 52(7): 1110-1118.
[3] BALDELLI R. Somatostatin analogues therapy in gastroenteropancreatic neuroendocrine tumours: current aspects and new perspectives. Front Endocrinol. 2014; 5: 7.
[4] MATHIAS CJ, GREEN M A & FLETCHER JW. Clinical PET/CT evaluation of patients with neuroendocrine cancer: experience with expanded access IND production and use of 68Ga-DOTA-NOC [document on line]. Indiana University Melvin and Bren Simon Cancer Center Cancer Research. Poster Presentation. May 21, 2015. http://imaging.medicine.iu.edu/research/office-for-research-imaging/office-for- research-imaging/forms-and-resources/expanded-access-acetate-and-ga- dota- noc/ overview-of-68ga-dota-noc-at-iu/.
[5] GREEN M, MATHIAS C & FLETCHER J. Preparation of 68Ga-DOTA-NOC for PET/CT evaluation of neuroendocrine tumors under an expanded access IND. J Nucl Med. 2014; 55 (supplement 1): 1144.
[6] VIS R, LAVALAYE J, VAN DE GARDE EM. GMP- compliant 68Ga radiolabelling in a conventional small-scale radiopharmacy: a feasible approach for routine clinical use. EJNMMI Research. 2015; 5: 27.
[7] RÖSCH F, PÉREZ-MALO M. Improved efficacy of synthesis of 68Ga radiopharmaceuticals in mixtures of aqueous solution and non-aqueous solvents. J Nucl Med. 2013; 54 (Supplement 2): 163.
[8] ZHERNOSEKOV KP, FILOSOFOV DV, BAUM RP, et. al. Processing of generator-produced 68Ga for medical application. J. Nucl. Med. 2007; 48(10): 1741-1748.
[9] PRUSZY?SKI M, MAJKOWSKA-PILIP A, LOKTIONOVA NS, et. al. Radio-labeling of DOTATOC with the long-lived positron emitter 44Sc. Appl. Rad. Isot. 2012; 70(6): 974-979.
[10] KUBICEK V, HAVLICKOVA J, KOTEK J, et. al. Gallium(III) complexes of DOTA and DOTA- monoamide: kinetic and termodinamic studies. Inorg. Chem., 2010; 49(23): 10960-10969.
[11] GREEN MA, WELCH MJ. Gallium radiopharmaceutical chemistry. Int J Rad Appl Instrum B. 1989; 16(5): 435-448.
[12] DE LEÓN-RODRÍGUEZ LM, KOVACS Z. The synthesis and chelation chemistry of DOTA ? peptide conjugates. Bioconjugate Chem. 2008; 19(2): 391-402.
[13] ANTUNES P, GINJ M, ZHANG H, et. al. Are radiogallium-labelled DOTA-conjugated somatostatin analogues superior to those labelled with other radiometals?. Eur.J. Nucl. Med. Mol. Imaging. 2007; 34(7): 982-993.
[14] CLARKE ET, MARTELL AE. Stabilities of trivalent metal ion complexes of the tetraacetate derivatives of 12-, 13-, and 14-membered tetraazamacrocycles. Inorg. Chim. Acta, 1992; 190(1): 37-46.
[15] BROCK JH, HALLIDAY J W, PIPPARD MJ & POWELL LW. Iron metabolism in health and disease. London: W B Saunders Co, 1994.
[16] MOERLEIN SM, WELCH MJ. The chemistry of gallium and indium as related to radiopharmaceutical production. Int. J. Nucl. Med. Biol. 1981; 8(4): 277-287.
[17] ZHANG Z. Bioinorganic chemistry of Aluminum, Gallium, and Indium complexes of 1-aryl-3-oxy-4-pyridinones [tesis on line] [doctoral thesis in philosophy]. University of British Columbia, december 1991. https://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0061723.