Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O -diethylethylenediamine-N,N -di-3-propanoate as potential tumour diagnostic agent
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2016
Authors
Lakić, MladenSabo, Ljubica
Ristic, Slavica
Savić, Aleksandar
Petricevic, Sasa
Nikolić, Nadežda S.
Vukadinović, Aleksandar
Janković, Drina
Sabo, Tibor J.
Vranješ-Đurić, Sanja
Article (Published version)
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The extensive development of radiopharmaceuticals towards early tumour detection and treatment has increased the demand for new ligands with higher tumour selectivity. Research has been done on the potential of the novel O,O-diethylethylenediamine-N,N-di-3-propanoate (L) ligand as a radionuclide vehicle for tumour targeting. Under alkaline conditions, L hydrolyses and produces half ester ligand (L) and diacid ligand (L), with characteristic donor atom array N, N, O. Ligand L was successfully labelled with Tc-99m at pH=9 by coordination with the octahedral fac-[Tc-99m(CO)(3)(H2O)(3)](+) intermediate, forming the main radioproduct fac-[(TcL)-Tc-99m(CO)(3)] (Tc1). The Tc-99m complex showed a low lipophilic character (log P = 0.48) and low binding affinity to human serum albumin (2.51 +/- 0.48%). In vitro stability studies in saline and human plasma, as well as challenge studies with cysteine and histidine, revealed high stability of the complex during 24 h. Biodistribution studies of Tc1 ...in female C57BL/6 mice bearing B16/F1 melanoma metastases showed significant tumour uptake: 9.81 +/- 1.19% ID g(-1) in the liver, 5.87 +/- 0.54% ID g(-1) in the lungs and 3.17 +/- 0.33% ID g(-1) in the ovary at 30 min post-injection. Favourable physicochemical properties, satisfactory in vitro/in vivo stability and biodistribution profile in the experimental metastatic melanoma model indicate the possible application of the radiolabelled ligand in tumour diagnosis. Copyright (C) 2015 John Wiley and Sons, Ltd.
Keywords:
eddp-type ligands / Tc-99m complex / Tc-99m carbonyl / metastatic melanoma / tumour diagnosisSource:
Applied Organometallic Chemistry, 2016, 30, 2, 81-88Funding / projects:
- Magnetic and radionuclide labeled nanostructured materials for medical applications (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-45015)
DOI: 10.1002/aoc.3401
ISSN: 0268-2605; 1099-0739
WoS: 000369872600003
Scopus: 2-s2.0-84955396715
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VinčaTY - JOUR AU - Lakić, Mladen AU - Sabo, Ljubica AU - Ristic, Slavica AU - Savić, Aleksandar AU - Petricevic, Sasa AU - Nikolić, Nadežda S. AU - Vukadinović, Aleksandar AU - Janković, Drina AU - Sabo, Tibor J. AU - Vranješ-Đurić, Sanja PY - 2016 UR - https://vinar.vin.bg.ac.rs/handle/123456789/273 AB - The extensive development of radiopharmaceuticals towards early tumour detection and treatment has increased the demand for new ligands with higher tumour selectivity. Research has been done on the potential of the novel O,O-diethylethylenediamine-N,N-di-3-propanoate (L) ligand as a radionuclide vehicle for tumour targeting. Under alkaline conditions, L hydrolyses and produces half ester ligand (L) and diacid ligand (L), with characteristic donor atom array N, N, O. Ligand L was successfully labelled with Tc-99m at pH=9 by coordination with the octahedral fac-[Tc-99m(CO)(3)(H2O)(3)](+) intermediate, forming the main radioproduct fac-[(TcL)-Tc-99m(CO)(3)] (Tc1). The Tc-99m complex showed a low lipophilic character (log P = 0.48) and low binding affinity to human serum albumin (2.51 +/- 0.48%). In vitro stability studies in saline and human plasma, as well as challenge studies with cysteine and histidine, revealed high stability of the complex during 24 h. Biodistribution studies of Tc1 in female C57BL/6 mice bearing B16/F1 melanoma metastases showed significant tumour uptake: 9.81 +/- 1.19% ID g(-1) in the liver, 5.87 +/- 0.54% ID g(-1) in the lungs and 3.17 +/- 0.33% ID g(-1) in the ovary at 30 min post-injection. Favourable physicochemical properties, satisfactory in vitro/in vivo stability and biodistribution profile in the experimental metastatic melanoma model indicate the possible application of the radiolabelled ligand in tumour diagnosis. Copyright (C) 2015 John Wiley and Sons, Ltd. T2 - Applied Organometallic Chemistry T1 - Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O -diethylethylenediamine-N,N -di-3-propanoate as potential tumour diagnostic agent VL - 30 IS - 2 SP - 81 EP - 88 DO - 10.1002/aoc.3401 ER -
@article{ author = "Lakić, Mladen and Sabo, Ljubica and Ristic, Slavica and Savić, Aleksandar and Petricevic, Sasa and Nikolić, Nadežda S. and Vukadinović, Aleksandar and Janković, Drina and Sabo, Tibor J. and Vranješ-Đurić, Sanja", year = "2016", abstract = "The extensive development of radiopharmaceuticals towards early tumour detection and treatment has increased the demand for new ligands with higher tumour selectivity. Research has been done on the potential of the novel O,O-diethylethylenediamine-N,N-di-3-propanoate (L) ligand as a radionuclide vehicle for tumour targeting. Under alkaline conditions, L hydrolyses and produces half ester ligand (L) and diacid ligand (L), with characteristic donor atom array N, N, O. Ligand L was successfully labelled with Tc-99m at pH=9 by coordination with the octahedral fac-[Tc-99m(CO)(3)(H2O)(3)](+) intermediate, forming the main radioproduct fac-[(TcL)-Tc-99m(CO)(3)] (Tc1). The Tc-99m complex showed a low lipophilic character (log P = 0.48) and low binding affinity to human serum albumin (2.51 +/- 0.48%). In vitro stability studies in saline and human plasma, as well as challenge studies with cysteine and histidine, revealed high stability of the complex during 24 h. Biodistribution studies of Tc1 in female C57BL/6 mice bearing B16/F1 melanoma metastases showed significant tumour uptake: 9.81 +/- 1.19% ID g(-1) in the liver, 5.87 +/- 0.54% ID g(-1) in the lungs and 3.17 +/- 0.33% ID g(-1) in the ovary at 30 min post-injection. Favourable physicochemical properties, satisfactory in vitro/in vivo stability and biodistribution profile in the experimental metastatic melanoma model indicate the possible application of the radiolabelled ligand in tumour diagnosis. Copyright (C) 2015 John Wiley and Sons, Ltd.", journal = "Applied Organometallic Chemistry", title = "Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O -diethylethylenediamine-N,N -di-3-propanoate as potential tumour diagnostic agent", volume = "30", number = "2", pages = "81-88", doi = "10.1002/aoc.3401" }
Lakić, M., Sabo, L., Ristic, S., Savić, A., Petricevic, S., Nikolić, N. S., Vukadinović, A., Janković, D., Sabo, T. J.,& Vranješ-Đurić, S.. (2016). Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O -diethylethylenediamine-N,N -di-3-propanoate as potential tumour diagnostic agent. in Applied Organometallic Chemistry, 30(2), 81-88. https://doi.org/10.1002/aoc.3401
Lakić M, Sabo L, Ristic S, Savić A, Petricevic S, Nikolić NS, Vukadinović A, Janković D, Sabo TJ, Vranješ-Đurić S. Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O -diethylethylenediamine-N,N -di-3-propanoate as potential tumour diagnostic agent. in Applied Organometallic Chemistry. 2016;30(2):81-88. doi:10.1002/aoc.3401 .
Lakić, Mladen, Sabo, Ljubica, Ristic, Slavica, Savić, Aleksandar, Petricevic, Sasa, Nikolić, Nadežda S., Vukadinović, Aleksandar, Janković, Drina, Sabo, Tibor J., Vranješ-Đurić, Sanja, "Synthesis and biological evaluation of Tc-99m tricarbonyl complex of O,O -diethylethylenediamine-N,N -di-3-propanoate as potential tumour diagnostic agent" in Applied Organometallic Chemistry, 30, no. 2 (2016):81-88, https://doi.org/10.1002/aoc.3401 . .