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
Ristić, Slavica
Savić, Aleksandar
Petričević, Saša
Nikolić, Nadežda
Vukadinović, Aleksandar
Janković, Drina
Sabo, Tibor
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 & Sons, Ltd.
Keywords:
eddp-type ligands / Tc-99m complex / Tc-99m carbonyl / metastatic melanoma / tumour diagnosisSource:
Applied Organometallic Chemistry, 2016, 30, 2, 81-88Publisher:
- Wiley, Hoboken
Funding / 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
WoS: 000369872600003
Scopus: 2-s2.0-84955396715
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Lakić, Mladen AU - Sabo, Ljubica AU - Ristić, Slavica AU - Savić, Aleksandar AU - Petričević, Saša AU - Nikolić, Nadežda AU - Vukadinović, Aleksandar AU - Janković, Drina AU - Sabo, Tibor AU - Vranješ-Đurić, Sanja PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2045 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 & Sons, Ltd. PB - Wiley, Hoboken 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 Ristić, Slavica and Savić, Aleksandar and Petričević, Saša and Nikolić, Nadežda and Vukadinović, Aleksandar and Janković, Drina and Sabo, Tibor 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 & Sons, Ltd.", publisher = "Wiley, Hoboken", 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., Ristić, S., Savić, A., Petričević, S., Nikolić, N., Vukadinović, A., Janković, D., Sabo, T.,& 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 Wiley, Hoboken., 30(2), 81-88. https://doi.org/10.1002/aoc.3401
Lakić M, Sabo L, Ristić S, Savić A, Petričević S, Nikolić N, Vukadinović A, Janković D, Sabo T, 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, Ristić, Slavica, Savić, Aleksandar, Petričević, Saša, Nikolić, Nadežda, Vukadinović, Aleksandar, Janković, Drina, Sabo, Tibor, 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 . .