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
Аутори
Stanković, DraganaJanković, Drina
Mirković, Marija
Radović, Magdalena
Milanović, Zorana
Vukadinović, Aleksandar
Stanković, Aljoša
Perić, Marko
Vranješ Đurić, Sanja
Prijović, Željko
Savić, Miroslav
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 z...bog 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.
Извор:
Arhiv za farmaciju, 2022, 72, 4 suplement, S428-S429Издавач:
- Savez farmaceutskih udruženja Srbije (SFUS)
Напомена:
- VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd
Институција/група
PharmacyTY - 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 .