The integration of fluorescence and plasmonic properties into one molecule is of importance in developing multifunctional imaging and therapy nanoprobes. The aim of this research was to evaluate the ...fluorescent properties and the plasmonic-photothermal, therapeutic, and radiotherapeutic potential of
Lu-dendrimer conjugated to folate and bombesin with gold nanoparticles in the dendritic cavity (
Lu-DenAuNP-folate-bombesin) when it is internalized in T47D breast cancer cells. The intense near-Infrared (NIR) fluorescence emitted at 825 nm from the conjugate inside cells corroborated the usefulness of DenAuNP-folate-bombesin for optical imaging. After laser irradiation, the presence of the nanosystem in cells caused a significant increase in the temperature of the medium (46.8°C, compared to 39.1°C without DenAuNP-folate-bombesin, P < 0.05), resulting in a significant decrease in cell viability (down to 16.51% ± 1.52%) due to the
Lu-DenAuNP-folate-bombesin plasmonic properties. After treatment with
Lu-DenAuNP-folate-bombesin, the T47D cell viability decreased 90% because of the radiation-absorbed dose (63.16 ± 4.20 Gy) delivered inside the cells. The
Lu-DenAuNP-folate-bombesin nanoprobe internalized in cancer cells exhibited properties suitable for optical imaging, plasmonic-photothermal therapy, and targeted radiotherapy.
Radiolabeled gold nanoparticles may function simultaneously as radiotherapy and thermal ablation systems. The gastrin‐releasing peptide receptor (GRP‐r) is overexpressed in prostate cancer, and Lys
3
...‐bombesin is a peptide that binds with high affinity to the GRP‐r. HIV Tat(49–57) is a cell‐penetrating peptide that reaches the DNA. In cancer cells,
177
Lu shows efficient crossfire effect, whereas
99m
Tc that is internalized in the cancer cell nuclei acts as an effective system of targeted radiotherapy because of the biological Auger effect. The aim of this research was to evaluate the
in vitro
potential of
99m
Tc‐labeled and
177
Lu‐labeled gold nanoparticles conjugated to Tat(49–57)‐Lys
3
‐bombesin peptides (
99m
Tc/
177
Lu‐AuNP‐Tat‐BN) as a plasmonic photothermal therapy and targeted radiotherapy system in PC3 prostate cancer cells. Peptides were conjugated to AuNPs (5 nm) by spontaneous reaction with the thiol group of cysteine (Cys). The effect on PC3 cell viability after laser heating of the AuNP‐Tat‐BN incubated with the cancer cells was conducted using an Nd:YAG laser pulsed for 5 ns at 532 nm (0.65 W/cm
2
). For the
99m
Tc/
177
Lu‐AuNP‐Tat‐BN to be obtained, the
177
Lu‐DOTA‐Gly‐Gly‐Cys and
99m
Tc‐HYNIC‐octreotide radiopeptides were first prepared and added simultaneously to a solution of AuNP‐Tat‐BN.
99m
Tc/
177
Lu‐AuNP‐Tat‐BN (20 Bq/cell) was incubated with PC3 cells, and the effect on the cell proliferation was evaluated after 3 days. Fluorescence images of
99m
Tc/
177
Lu‐AuNP‐Tat‐BN internalized in nuclei of PC3 were also obtained. After laser irradiation, the presence of AuNP‐Tat‐BN caused a significant increase in the temperature of the medium (46.4 vs 39.5 °C of that without AuNP) resulting in a significant decrease in PC3 cell viability down to 1.3%. After treatment with
99m
Tc/
177
Lu‐AuNP‐Tat‐BN, the PC3 cell proliferation was inhibited. The nanosystem exhibited properties suitable for plasmonic photothermal therapy and targeted radiotherapy in the treatment of prostate cancer.
Abstract The α(ν)β(3) integrin is over-expressed in the tumor neovasculature and the tumor cells of glioblastomas. The HIV Tat-derived peptide has been used to deliver various cargos into cells. The ...aim of this research was to synthesize and assess the in vitro and in vivo uptake of99m Tc-N2 S2 -Tat(49–57)-c(RGDyK) (99m Tc-Tat-RGD) in α(ν)β(3) integrin positive cancer cells and compare it to that of a conventional99m Tc-RGD peptide (99m Tc-EDDA/HYNIC-E-c(RGDfK)2 ). Methods: The c(RGDyK) peptide was conjugated to a maleimidopropionyl (MP) moiety through Lys, and the MP group was used as the branch position to form a thioether with the Cys12 side chain of the Tat(49–57)-spacer-N2 S2 peptide.99m Tc-Tat-RGD was prepared, and stability studies were carried out by size exclusion HPLC analyses in human serum. The in vitro affinity for α(v)β(3) integrin was determined by a competitive binding assay. In vitro internalization was determined using glioblastoma C6 cells. Biodistribution studies were accomplished in athymic mice with C6 induced tumors that had blocked and unblocked receptors. Images were obtained using a micro-SPECT/CT. Results :99m Tc-Tat-RGD was obtained with a radiochemical purity higher than 95%, as determined by radio-HPLC and ITLC-SG analyses. Protein binding was 15.7% for99m Tc-Tat-RGD and 5.6% for99m Tc-RGD. The IC50 values were 6.7 nM (99m Tc-Tat-RGD) and 4.6 nM (99m Tc-RGD). Internalization in C6 cells was higher in99m Tc-Tat-RGD (37.5%) than in99m Tc-RGD (10%). Biodistribution studies and in vivo micro-SPECT/CT images in mice showed higher tumor uptake for99m Tc-Tat-RGD (6.98% ± 1.34% ID/g at 3 h) than that of99m Tc-RGD (3.72% ± 0.52% ID/g at 3 h) with specific recognition for α(v)β(3) integrins. Conclusions : Because of the significant cell internalization (Auger and internal conversion electrons) and specific recognition for α(v)β(3) integrins, the hybrid99m Tc-N2 S2 -Tat(49–57)-c(RGDyK) radiopharmaceutical is potentially useful for the imaging and possible therapy of tumors expressing α(v)β(3) integrins.
The alpha(I12)beta(3) integrin is over-expressed in the tumor neovasculature and the tumor cells of glioblastomas. The HIV Tat-derived peptide has been used to deliver various cargos into cells. The ...aim of this research was to synthesize and assess the in vitro and in vivo uptake of 99mTc-N2S2-Tat(49a57)-c(RGDyK) (99mTc-Tat-RGD) in alpha(I12)beta(3) integrin positive cancer cells and compare it to that of a conventional 99mTc-RGD peptide (99mTc-EDDA/HYNIC-E-c(RGDfK)2). Methods: The c(RGDyK) peptide was conjugated to a maleimidopropionyl (MP) moiety through Lys, and the MP group was used as the branch position to form a thioether with the Cys12 side chain of the Tat(49a57)-spacer-N2S2 peptide. 99mTc-Tat-RGD was prepared, and stability studies were carried out by size exclusion HPLC analyses in human serum. The in vitro affinity for alpha(v)beta(3) integrin was determined by a competitive binding assay. In vitro internalization was determined using glioblastoma C6 cells. Biodistribution studies were accomplished in athymic mice with C6 induced tumors that had blocked and unblocked receptors. Images were obtained using a micro-SPECT/CT. Results: 99mTc-Tat-RGD was obtained with a radiochemical purity higher than 95%, as determined by radio-HPLC and ITLC-SG analyses. Protein binding was 15.7% for 99mTc-Tat-RGD and 5.6% for 99mTc-RGD. The IC50 values were 6.7 nM (99mTc-Tat-RGD) and 4.6 nM (99mTc-RGD). Internalization in C6 cells was higher in 99mTc-Tat-RGD (37.5%) than in 99mTc-RGD (10%). Biodistribution studies and in vivo micro-SPECT/CT images in mice showed higher tumor uptake for 99mTc-Tat-RGD (6.98% +/- 1.34% ID/g at 3 h) than that of 99mTc-RGD (3.72% +/- 0.52% ID/g at 3 h) with specific recognition for alpha(v)beta(3) integrins. Conclusions: Because of the significant cell internalization (Auger and internal conversion electrons) and specific recognition for alpha(v)beta(3) integrins, the hybrid 99mTc-N2S2-Tat(49a57)-c(RGDyK) radiopharmaceutical is potentially useful for the imaging and possible therapy of tumors expressing alpha(v)beta(3) integrins.
The aim of this research was to evaluate the in vitro potential of 177Lu-labeled gold nanoparticles conjugated to cyclo-RGDfK(C) peptides (177Lu-AuNP-cRGDfK(C)) as a plasmonic photothermal therapy ...and targeted radiotherapy system in MCF7 breast cancer cells. Peptides were conjugated to AuNPs (20 nm) by spontaneous reaction with the thiol group of cysteine (C). After laser irradiation, the presence of cRGDfK(C)-AuNP in cells caused a significant increase in the temperature of the medium (50.5 °C, compared to 40.3 °C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with 177Lu-AuNP-cRGDfK(C), the MCF7 cell proliferation was significantly inhibited.
Sm-HM for arthritic knee pain. Estimated dosimetry Hardy-Pérez, Alberto E; Torres-García, Eugenio; Arteaga-de-Murphy, Consuelo ...
Australasian physical & engineering sciences in medicine,
03/2012, Letnik:
35, Številka:
1
Journal Article
Osteoarthritis is the most common type of arthropathy and after cardiovascular diseases is the most disabling disease in developing countries. The dosimetry for the clinical application of ...153-samarium-hydroxymacroaggregates (¹⁵³Sm-HM) for radiation synovectomy (RSV) and palliative treatment for arthritic pain, as far as we know, has not been reported. The aim of this research was to estimate the radiation dose necessary for synovial ablation and pain palliation with minimum risk to the patient. ¹⁵³Sm-HM (370 MBq) was administered intra-articularly in a patient with severe knee pain and hindered motility. Regions of interest drawn on sequential, conjugated, anterior and posterior scintigraphy images were used to obtain the respective activity. The data was entered into a knee joint histological-geometric model designed with micrometric dimensions to represent the synovial cell layers. The Monte Carlo code was used to calculate the absorbed dose in each of the 12 model-cells representing the distance from the synovial liquid to the cartilage or bone. The absorbed dose in the synovial cavity was 114 Gy which is sufficient energy for RSV. The treated patient referred little pain and higher motility with no adverse reactions. ¹⁵³Sm-HM is a potentially valid radiopharmaceutical for RSV, which effectively palliates knee pain.
sup 153^Sm-HM for arthritic knee pain. Estimated dosimetry Hardy-pérez, Alberto E; Torres-garcía, Eugenio; Arteaga-de-murphy, Consuelo ...
Australasian physical & engineering sciences in medicine,
03/2012, Letnik:
35, Številka:
1
Journal Article
Osteoarthritis is the most common type of arthropathy and after cardiovascular diseases is the most disabling disease in developing countries. The dosimetry for the clinical application of ...153-samarium-hydroxymacroaggregates (^sup 153^Sm-HM) for radiation synovectomy (RSV) and palliative treatment for arthritic pain, as far as we know, has not been reported. The aim of this research was to estimate the radiation dose necessary for synovial ablation and pain palliation with minimum risk to the patient. ^sup 153^Sm-HM (370 MBq) was administered intra-articularly in a patient with severe knee pain and hindered motility. Regions of interest drawn on sequential, conjugated, anterior and posterior scintigraphy images were used to obtain the respective activity. The data was entered into a knee joint histological-geometric model designed with micrometric dimensions to represent the synovial cell layers. The Monte Carlo code was used to calculate the absorbed dose in each of the 12 model-cells representing the distance from the synovial liquid to the cartilage or bone. The absorbed dose in the synovial cavity was 114 Gy which is sufficient energy for RSV. The treated patient referred little pain and higher motility with no adverse reactions. ^sup 153^Sm-HM is a potentially valid radiopharmaceutical for RSV, which effectively palliates knee pain.PUBLICATION ABSTRACT
153Sm-HM for arthritic knee pain. Estimated dosimetry Hardy-Pérez, Alberto E.; Torres-García, Eugenio; Arteaga-de-Murphy, Consuelo ...
Australasian physical & engineering sciences in medicine,
3/2012, Letnik:
35, Številka:
1
Journal Article
Osteoarthritis is the most common type of arthropathy and after cardiovascular diseases is the most disabling disease in developing countries. The dosimetry for the clinical application of ...153-samarium-hydroxymacroaggregates (
153
Sm-HM) for radiation synovectomy (RSV) and palliative treatment for arthritic pain, as far as we know, has not been reported. The aim of this research was to estimate the radiation dose necessary for synovial ablation and pain palliation with minimum risk to the patient.
153
Sm-HM (370 MBq) was administered intra-articularly in a patient with severe knee pain and hindered motility. Regions of interest drawn on sequential, conjugated, anterior and posterior scintigraphy images were used to obtain the respective activity. The data was entered into a knee joint histological-geometric model designed with micrometric dimensions to represent the synovial cell layers. The Monte Carlo code was used to calculate the absorbed dose in each of the 12 model-cells representing the distance from the synovial liquid to the cartilage or bone. The absorbed dose in the synovial cavity was 114 Gy which is sufficient energy for RSV. The treated patient referred little pain and higher motility with no adverse reactions.
153
Sm-HM is a potentially valid radiopharmaceutical for RSV, which effectively palliates knee pain.
