177Lu-doxycycline as potential radiopharmaceutical: electrochemical characterization, radiolabeling, and biodistribution in tumor-bearing mice
Нема приказа
Аутори
Milanović, ZoranaJanković, Drina
Vranješ-Đurić, Sanja
Radović, Magdalena
Prijović, Željko
Zavišić, Gordana
Perić, Marko
Stanković, Dalibor M.
Mirković, Marija D.
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Purpose Recent studies with doxycycline as adjuvant therapy to conventional chemotherapy have shown promising results in cancer therapy. The current study aimed to examine the capability of 177Lu-labeled tetracycline ligand, doxycycline hyclate, to use as an anticancer agent.Materials and methods Doxycycline was radiolabeled with beta-emitting radioisotope 177Lu. Complex formation and its interaction with DNA were investigated electrochemically. Binding of 177Lu-doxycycline to CT 26 cell line was done. Biodistribution of 177Lu-doxycycline was examined in healthy Wistar rats and CT26 colon carcinoma tumor-bearing mice by i.v. and i.p. administration, respectively.Results Doxycycline hyclate was successfully radiolabeled with 177Lu in high radiolabeling yield (>99%). The radiolabeled complex was stable in vitro in saline and human serum over 72 h. Non-radioactive Lu-doxycycline complex formation was demonstrated electrochemically as well. Intercalative interactions of the doxycycline and... Lu-doxycycline with DNA were proved using simultaneously spectrophotometric and electrochemical methods. The binding of the radiolabeled complex with plasma proteins was 4.0 ± 0.4%. The partition coefficient showed the lipophilic nature of the complex similar to the free ligand. The binding curve demonstrates binding from 0.1 nM concentrations of 177Lu-doxycycline, with half-binding estimated ∼100 nM. Biodistribution studies of 177Lu-doxycycline in CT26 colon tumor-bearing mice showed a satisfactory accumulation rate in the tumor (2.88 ± 0.85% ID/g) 3 h after intraperitoneal injection. Both the hepatobiliary system and the urinary system were prominent as excretory routes of the radiolabeled complex.Conclusion Considering obtained results, 177Lu-doxycycline complex, due to its excellent electrochemical and biological characteristics, with emphasis on the binding ability to DNA via intercalative interaction as well as significant accumulation in the tumor, is suitable for further in vivo studies to investigate its potential use in cancer treatment.
Кључне речи:
177Lu / cancer therapy / DNA intercalator / doxycycline / radiolabelingИзвор:
International Journal of Radiation Biology, 2021, 1-9
DOI: 10.1080/09553002.2021.1976864
ISSN: 0955-3002
PubMed: 34473599
WoS: 000698278700001
Scopus: 2-s2.0-85115653872
Институција/група
VinčaTY - JOUR AU - Milanović, Zorana AU - Janković, Drina AU - Vranješ-Đurić, Sanja AU - Radović, Magdalena AU - Prijović, Željko AU - Zavišić, Gordana AU - Perić, Marko AU - Stanković, Dalibor M. AU - Mirković, Marija D. PY - 2021 UR - https://vinar.vin.bg.ac.rs/handle/123456789/9960 AB - Purpose Recent studies with doxycycline as adjuvant therapy to conventional chemotherapy have shown promising results in cancer therapy. The current study aimed to examine the capability of 177Lu-labeled tetracycline ligand, doxycycline hyclate, to use as an anticancer agent.Materials and methods Doxycycline was radiolabeled with beta-emitting radioisotope 177Lu. Complex formation and its interaction with DNA were investigated electrochemically. Binding of 177Lu-doxycycline to CT 26 cell line was done. Biodistribution of 177Lu-doxycycline was examined in healthy Wistar rats and CT26 colon carcinoma tumor-bearing mice by i.v. and i.p. administration, respectively.Results Doxycycline hyclate was successfully radiolabeled with 177Lu in high radiolabeling yield (>99%). The radiolabeled complex was stable in vitro in saline and human serum over 72 h. Non-radioactive Lu-doxycycline complex formation was demonstrated electrochemically as well. Intercalative interactions of the doxycycline and Lu-doxycycline with DNA were proved using simultaneously spectrophotometric and electrochemical methods. The binding of the radiolabeled complex with plasma proteins was 4.0 ± 0.4%. The partition coefficient showed the lipophilic nature of the complex similar to the free ligand. The binding curve demonstrates binding from 0.1 nM concentrations of 177Lu-doxycycline, with half-binding estimated ∼100 nM. Biodistribution studies of 177Lu-doxycycline in CT26 colon tumor-bearing mice showed a satisfactory accumulation rate in the tumor (2.88 ± 0.85% ID/g) 3 h after intraperitoneal injection. Both the hepatobiliary system and the urinary system were prominent as excretory routes of the radiolabeled complex.Conclusion Considering obtained results, 177Lu-doxycycline complex, due to its excellent electrochemical and biological characteristics, with emphasis on the binding ability to DNA via intercalative interaction as well as significant accumulation in the tumor, is suitable for further in vivo studies to investigate its potential use in cancer treatment. T2 - International Journal of Radiation Biology T1 - 177Lu-doxycycline as potential radiopharmaceutical: electrochemical characterization, radiolabeling, and biodistribution in tumor-bearing mice SP - 1 EP - 9 DO - 10.1080/09553002.2021.1976864 ER -
@article{ author = "Milanović, Zorana and Janković, Drina and Vranješ-Đurić, Sanja and Radović, Magdalena and Prijović, Željko and Zavišić, Gordana and Perić, Marko and Stanković, Dalibor M. and Mirković, Marija D.", year = "2021", abstract = "Purpose Recent studies with doxycycline as adjuvant therapy to conventional chemotherapy have shown promising results in cancer therapy. The current study aimed to examine the capability of 177Lu-labeled tetracycline ligand, doxycycline hyclate, to use as an anticancer agent.Materials and methods Doxycycline was radiolabeled with beta-emitting radioisotope 177Lu. Complex formation and its interaction with DNA were investigated electrochemically. Binding of 177Lu-doxycycline to CT 26 cell line was done. Biodistribution of 177Lu-doxycycline was examined in healthy Wistar rats and CT26 colon carcinoma tumor-bearing mice by i.v. and i.p. administration, respectively.Results Doxycycline hyclate was successfully radiolabeled with 177Lu in high radiolabeling yield (>99%). The radiolabeled complex was stable in vitro in saline and human serum over 72 h. Non-radioactive Lu-doxycycline complex formation was demonstrated electrochemically as well. Intercalative interactions of the doxycycline and Lu-doxycycline with DNA were proved using simultaneously spectrophotometric and electrochemical methods. The binding of the radiolabeled complex with plasma proteins was 4.0 ± 0.4%. The partition coefficient showed the lipophilic nature of the complex similar to the free ligand. The binding curve demonstrates binding from 0.1 nM concentrations of 177Lu-doxycycline, with half-binding estimated ∼100 nM. Biodistribution studies of 177Lu-doxycycline in CT26 colon tumor-bearing mice showed a satisfactory accumulation rate in the tumor (2.88 ± 0.85% ID/g) 3 h after intraperitoneal injection. Both the hepatobiliary system and the urinary system were prominent as excretory routes of the radiolabeled complex.Conclusion Considering obtained results, 177Lu-doxycycline complex, due to its excellent electrochemical and biological characteristics, with emphasis on the binding ability to DNA via intercalative interaction as well as significant accumulation in the tumor, is suitable for further in vivo studies to investigate its potential use in cancer treatment.", journal = "International Journal of Radiation Biology", title = "177Lu-doxycycline as potential radiopharmaceutical: electrochemical characterization, radiolabeling, and biodistribution in tumor-bearing mice", pages = "1-9", doi = "10.1080/09553002.2021.1976864" }
Milanović, Z., Janković, D., Vranješ-Đurić, S., Radović, M., Prijović, Ž., Zavišić, G., Perić, M., Stanković, D. M.,& Mirković, M. D.. (2021). 177Lu-doxycycline as potential radiopharmaceutical: electrochemical characterization, radiolabeling, and biodistribution in tumor-bearing mice. in International Journal of Radiation Biology, 1-9. https://doi.org/10.1080/09553002.2021.1976864
Milanović Z, Janković D, Vranješ-Đurić S, Radović M, Prijović Ž, Zavišić G, Perić M, Stanković DM, Mirković MD. 177Lu-doxycycline as potential radiopharmaceutical: electrochemical characterization, radiolabeling, and biodistribution in tumor-bearing mice. in International Journal of Radiation Biology. 2021;:1-9. doi:10.1080/09553002.2021.1976864 .
Milanović, Zorana, Janković, Drina, Vranješ-Đurić, Sanja, Radović, Magdalena, Prijović, Željko, Zavišić, Gordana, Perić, Marko, Stanković, Dalibor M., Mirković, Marija D., "177Lu-doxycycline as potential radiopharmaceutical: electrochemical characterization, radiolabeling, and biodistribution in tumor-bearing mice" in International Journal of Radiation Biology (2021):1-9, https://doi.org/10.1080/09553002.2021.1976864 . .