TY  - JOUR
AU  - Stanković, Dragana
AU  - Radović, Magdalena
AU  - Stanković, Aljoša
AU  - Mirković, Marija
AU  - Vukadinović, Aleksandar
AU  - Mijović, Milica
AU  - Milanović, Zorana
AU  - Ognjanović, Miloš
AU  - Janković, Drina
AU  - Antić, Bratislav
AU  - Vranješ-Đurić, Sanja
AU  - Savić, Miroslav
AU  - Prijović, Željko
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4962
AB  - As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiola- beled with Lutetium-177 (177Lu), generating 177Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by 177Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 μg/50 μL of 177Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 μg/50 μL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 μg/50 μL did not significantly benefit the therapy. Histopathology analysis revealed that the 177Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, 177Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy.
PB  - MDPI
T2  - Pharmaceutics
T1  - Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors
VL  - 15
IS  - 7
DO  - 10.3390/pharmaceutics15071943
ER  - 

@article{
author = "Stanković, Dragana and Radović, Magdalena and Stanković, Aljoša and Mirković, Marija and Vukadinović, Aleksandar and Mijović, Milica and Milanović, Zorana and Ognjanović, Miloš and Janković, Drina and Antić, Bratislav and Vranješ-Đurić, Sanja and Savić, Miroslav and Prijović, Željko",
year = "2023",
abstract = "As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiola- beled with Lutetium-177 (177Lu), generating 177Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by 177Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 μg/50 μL of 177Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 μg/50 μL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 μg/50 μL did not significantly benefit the therapy. Histopathology analysis revealed that the 177Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, 177Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors",
volume = "15",
number = "7",
doi = "10.3390/pharmaceutics15071943"
}

Stanković, D., Radović, M., Stanković, A., Mirković, M., Vukadinović, A., Mijović, M., Milanović, Z., Ognjanović, M., Janković, D., Antić, B., Vranješ-Đurić, S., Savić, M.,& Prijović, Ž.. (2023). Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors. in Pharmaceutics
MDPI., 15(7).
https://doi.org/10.3390/pharmaceutics15071943

Stanković D, Radović M, Stanković A, Mirković M, Vukadinović A, Mijović M, Milanović Z, Ognjanović M, Janković D, Antić B, Vranješ-Đurić S, Savić M, Prijović Ž. Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors. in Pharmaceutics. 2023;15(7).
doi:10.3390/pharmaceutics15071943 .

Stanković, Dragana, Radović, Magdalena, Stanković, Aljoša, Mirković, Marija, Vukadinović, Aleksandar, Mijović, Milica, Milanović, Zorana, Ognjanović, Miloš, Janković, Drina, Antić, Bratislav, Vranješ-Đurić, Sanja, Savić, Miroslav, Prijović, Željko, "Synthesis, Characterization, and Therapeutic Efficacy of 177Lu-DMSA@SPIONs in Nanobrachytherapy of Solid Tumors" in Pharmaceutics, 15, no. 7 (2023),
https://doi.org/10.3390/pharmaceutics15071943 . .

TY  - CONF
AU  - Stanković, Dragana
AU  - Janković, Drina
AU  - Mirković, Marija
AU  - Radović, Magdalena
AU  - Milanović, Zorana
AU  - Vukadinović, Aleksandar
AU  - Stanković, Aljoša
AU  - Perić, Marko
AU  - Vranješ Đurić, Sanja
AU  - Prijović, Željko
AU  - Savić, Miroslav
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4576
AB  - Nanoparticle delivery to solid tumors after an intravenous injection has shown to be
very limited in its ability to achieve therapeutic dosage in the tumor due to nonspecific
nanoparticle uptake by RES. To overcome these problems, local intratumoral injection of
nanoparticles is being investigated as more relevant route of administration. In the present
study, superparamagnetic iron oxide nanoparticles (SPIONs) were synthetized, coated with
citric (CA) or dimercaptosuccinic acid (DMSA) and radiolabeled with 90 Y or 177Lu, aiming to
develop radioactive nanoparticles for localized tumor therapy. Biodistribution and
antitumor efficacy of radiolabeled SPIONs after local intratumoral administration in CT26 or
4T1 xenografts-bearing BALB/c mice were studied. Tracking the radioactivity distribution of
injected 90 Y-CA-SPIONs and 177Lu-DMSA-SPIONs revealed that due to the size of the
nanoparticles, their diffusive escape from the tumor into healthy organs and tissues is
slowed down; the particles remain at the injection site up to 14 days after the injection, and
thereby increasing the tumor's exposure to radiation. Lower therapeutic efficacy of 177Lu-
DMSA-SPIONs in CT26 or 4T1 tumor can be explained by slight diffusion of particles from
injection sites into distant tumor regions and moderate-energy β-particles emitted by 177 Lu
(0.5MeV). These studies suggest that 90Y-CA-SPIONs is superior to 177 Lu-DMSA-SPIONs at
inhibiting both tumors growth, due to the high-energy β-particles emitted by 90 Y (2.27MeV)
and a longer path length. 90 Y is therapeutically superior to 177Lu in investigated xenograft
models. We believe that an intratumorally injected radiolabeled SPIONs can be considered as
a potential therapeutic agent for localized cancer therapy.
AB  - Prethodna istraživanja su pokazala da se intravenskim načinom aplikacije nanočestica
ne postiže zadovoljavajuća terapijska doza u solidnim tumorima, zbog nespecifičnog
preuzimanja nanočestica od strane retikuloendotelnog sistema. Da bi se prevazišli ovi
problemi, smatra se da je intratumorski način aplikacije pogodniji način primene nanočestica
u terapiji solidnih tumora. Sa ciljem da se razvije radiofarmaceutik za lokalizovanu terapiju
tumora, u ovim ispitivanjima, superparamagnetne nanočestice oksida gvožđa (SPION) su
sintetisane, površinski obložene limunskom (CA) i dimerkaptoćilibarnom (DMSA) kiselinom
i radioobeležene sa 90 Y i 177 Lu. Posebna pažnja je posvećena ispitivanjima distribucije i
antitumorske efikasnosti radioaktivno obeleženih SPIONa nakon lokalne intratumorske
primene u ksenografte indukovane supkutanim injekcijama CT26 i 4T1 ćelija BALB/c
miševima. Praćenje distribucije intratumorski injektovanih 90 Y-CA-SPION-a i 177 Lu-DMSA-
SPION-a je pokazalo da je zbog veličine nanočestica njihova migracija iz tumorskog tkiva u
zdrave organe i tkiva usporena, pa čestice ostaju na mestu ubrizgavanja do 14 dana, čime se
značajno povećava izloženost tumora zračenju. Niža terapijska efikasnost 177Lu-DMSA-
SPION-a u CT26 ili 4T1 tumorima se može objasniti slabom migracijom čestica sa mesta
aplikacije do udaljenih tumorskih ćelija kao i kratkim dometom u tkivu β– čestica koje
emituje 177 Lu zbog energije zračenja od 0,5MeV. Ova ispitivanja su pokazala da je 90 Y-CA-
SPION značajno efikasniji od 177 Lu-DMSA-SPION u inhibiciji rasta obe vrste tumora, zbog
visokoenergetskih β– čestica koje emituje 90 Y (2,27MeV) i većeg dometa u tkivu. 90 Y je
terapeutski superiorniji od 177 Lu u istraživanim modelima ksenografta. Mišljenja smo da se
intratumorski primenjeni radioaktivno obeleženi SPION-i mogu smatrati potencijalnim
terapijskim agensom za lokalizovanu terapiju solidnih, inoperabilnih i teško dostupnih
tumora.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Efficacy of 177Lu- and 90Y-labeled nanoparticles in targeted tumor therapy in a mouse CT26 and 4T1 xenograft model
T1  - Efikasnost 177Lu‐ i 90 Y‐obeleženih nanočestica u ciljanoj terapiji tumora na modelu mišjih CT26 I 4T1 ksenografta
VL  - 72
IS  - 4 suplement
SP  - S428
EP  - S429
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4576
ER  - 

@conference{
author = "Stanković, Dragana and Janković, Drina and Mirković, Marija and Radović, Magdalena and Milanović, Zorana and Vukadinović, Aleksandar and Stanković, Aljoša and Perić, Marko and Vranješ Đurić, Sanja and Prijović, Željko and Savić, Miroslav",
year = "2022",
abstract = "Nanoparticle delivery to solid tumors after an intravenous injection has shown to be
very limited in its ability to achieve therapeutic dosage in the tumor due to nonspecific
nanoparticle uptake by RES. To overcome these problems, local intratumoral injection of
nanoparticles is being investigated as more relevant route of administration. In the present
study, superparamagnetic iron oxide nanoparticles (SPIONs) were synthetized, coated with
citric (CA) or dimercaptosuccinic acid (DMSA) and radiolabeled with 90 Y or 177Lu, aiming to
develop radioactive nanoparticles for localized tumor therapy. Biodistribution and
antitumor efficacy of radiolabeled SPIONs after local intratumoral administration in CT26 or
4T1 xenografts-bearing BALB/c mice were studied. Tracking the radioactivity distribution of
injected 90 Y-CA-SPIONs and 177Lu-DMSA-SPIONs revealed that due to the size of the
nanoparticles, their diffusive escape from the tumor into healthy organs and tissues is
slowed down; the particles remain at the injection site up to 14 days after the injection, and
thereby increasing the tumor's exposure to radiation. Lower therapeutic efficacy of 177Lu-
DMSA-SPIONs in CT26 or 4T1 tumor can be explained by slight diffusion of particles from
injection sites into distant tumor regions and moderate-energy β-particles emitted by 177 Lu
(0.5MeV). These studies suggest that 90Y-CA-SPIONs is superior to 177 Lu-DMSA-SPIONs at
inhibiting both tumors growth, due to the high-energy β-particles emitted by 90 Y (2.27MeV)
and a longer path length. 90 Y is therapeutically superior to 177Lu in investigated xenograft
models. We believe that an intratumorally injected radiolabeled SPIONs can be considered as
a potential therapeutic agent for localized cancer therapy., Prethodna istraživanja su pokazala da se intravenskim načinom aplikacije nanočestica
ne postiže zadovoljavajuća terapijska doza u solidnim tumorima, zbog nespecifičnog
preuzimanja nanočestica od strane retikuloendotelnog sistema. Da bi se prevazišli ovi
problemi, smatra se da je intratumorski način aplikacije pogodniji način primene nanočestica
u terapiji solidnih tumora. Sa ciljem da se razvije radiofarmaceutik za lokalizovanu terapiju
tumora, u ovim ispitivanjima, superparamagnetne nanočestice oksida gvožđa (SPION) su
sintetisane, površinski obložene limunskom (CA) i dimerkaptoćilibarnom (DMSA) kiselinom
i radioobeležene sa 90 Y i 177 Lu. Posebna pažnja je posvećena ispitivanjima distribucije i
antitumorske efikasnosti radioaktivno obeleženih SPIONa nakon lokalne intratumorske
primene u ksenografte indukovane supkutanim injekcijama CT26 i 4T1 ćelija BALB/c
miševima. Praćenje distribucije intratumorski injektovanih 90 Y-CA-SPION-a i 177 Lu-DMSA-
SPION-a je pokazalo da je zbog veličine nanočestica njihova migracija iz tumorskog tkiva u
zdrave organe i tkiva usporena, pa čestice ostaju na mestu ubrizgavanja do 14 dana, čime se
značajno povećava izloženost tumora zračenju. Niža terapijska efikasnost 177Lu-DMSA-
SPION-a u CT26 ili 4T1 tumorima se može objasniti slabom migracijom čestica sa mesta
aplikacije do udaljenih tumorskih ćelija kao i kratkim dometom u tkivu β– čestica koje
emituje 177 Lu zbog energije zračenja od 0,5MeV. Ova ispitivanja su pokazala da je 90 Y-CA-
SPION značajno efikasniji od 177 Lu-DMSA-SPION u inhibiciji rasta obe vrste tumora, zbog
visokoenergetskih β– čestica koje emituje 90 Y (2,27MeV) i većeg dometa u tkivu. 90 Y je
terapeutski superiorniji od 177 Lu u istraživanim modelima ksenografta. Mišljenja smo da se
intratumorski primenjeni radioaktivno obeleženi SPION-i mogu smatrati potencijalnim
terapijskim agensom za lokalizovanu terapiju solidnih, inoperabilnih i teško dostupnih
tumora.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Efficacy of 177Lu- and 90Y-labeled nanoparticles in targeted tumor therapy in a mouse CT26 and 4T1 xenograft model, Efikasnost 177Lu‐ i 90 Y‐obeleženih nanočestica u ciljanoj terapiji tumora na modelu mišjih CT26 I 4T1 ksenografta",
volume = "72",
number = "4 suplement",
pages = "S428-S429",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4576"
}

Stanković, D., Janković, D., Mirković, M., Radović, M., Milanović, Z., Vukadinović, A., Stanković, A., Perić, M., Vranješ Đurić, S., Prijović, Ž.,& Savić, M.. (2022). Efficacy of 177Lu- and 90Y-labeled nanoparticles in targeted tumor therapy in a mouse CT26 and 4T1 xenograft model. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S428-S429.
https://hdl.handle.net/21.15107/rcub_farfar_4576

Stanković D, Janković D, Mirković M, Radović M, Milanović Z, Vukadinović A, Stanković A, Perić M, Vranješ Đurić S, Prijović Ž, Savić M. Efficacy of 177Lu- and 90Y-labeled nanoparticles in targeted tumor therapy in a mouse CT26 and 4T1 xenograft model. in Arhiv za farmaciju. 2022;72(4 suplement):S428-S429.
https://hdl.handle.net/21.15107/rcub_farfar_4576 .

Stanković, Dragana, Janković, Drina, Mirković, Marija, Radović, Magdalena, Milanović, Zorana, Vukadinović, Aleksandar, Stanković, Aljoša, Perić, Marko, Vranješ Đurić, Sanja, Prijović, Željko, Savić, Miroslav, "Efficacy of 177Lu- and 90Y-labeled nanoparticles in targeted tumor therapy in a mouse CT26 and 4T1 xenograft model" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S428-S429,
https://hdl.handle.net/21.15107/rcub_farfar_4576 .