Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers. 68Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. ...The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare 99mTc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (99mTc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the 99mTc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer.
99mTc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous 68Ga-PSMA-617scan) were acquired at 1h and 3h after 99mTc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%.
In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of 99mTc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as 68Ga-PSMA-617 does.
The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of 99mTc-EDDA/HYNIC-iPSMA.
Prostate-specific membrane antigen (PSMA) is highly over-expressed in advanced prostate cancers.
Ga-labeled PSMA inhibitors (iPSMA) are currently used for prostate cancer detection by PET imaging. ...The availability of simple, efficient and reproducible radiolabeling procedures is essential for developing new SPECT radiopharmaceuticals for clinical translation. The aim of this research was to prepare
Tc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (
Tc-EDDA/HYNIC-iPSMA) obtained from lyophilized kit formulations and evaluate the in vitro and in vivo radiopharmaceutical binding to prostate cancer cells over-expressing PSMA, as well as the
Tc-EDDA/HYNIC-iPSMA normal biodistribution in humans and the preliminary uptake in patients with prostate cancer.
Tc labeling was performed by adding sodium pertechnetate solution and a 0.2M phosphate buffer (pH 7.0) to a lyophilized formulation containing HYNIC-iPSMA, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated by reversed-phase HPLC and ITLC-SG analyses. Stability studies in human serum were performed by size-exclusion HPLC. In vitro cell uptake was tested using prostate cancer cells (LNCaP) with blocked and non-blocked receptors. Biodistribution and tumor uptake were determined in LNCaP tumor-bearing nude mice with blocked and non-blocked receptors, and images were obtained using a micro-SPECT/CT. Whole-body images from three healthy men and two patients with histologically-confirmed prostate cancer (one of them with a previous
Ga-PSMA-617scan) were acquired at 1h and 3h after
Tc-EDDA/HYNIC-iPSMA administration with radiochemical purities of >98%.
In vitro and in vivo studies showed high radiopharmaceutical stability in human serum, specific recognition for PSMA, high tumor uptake (10.22±2.96% ID/g at 1h) with rapid blood clearance and mainly kidney elimination. Preliminary images in patients demonstrated the ability of
Tc-EDDA/HYNIC-iPSMA to detect tumors and metastases of prostate cancer as well as
Ga-PSMA-617 does.
The results obtained in this study warrant further dosimetry and clinical studies to determine the specificity and sensitivity of
Tc-EDDA/HYNIC-iPSMA.
This research aimed to assess the radiation absorbed dose produced by
Lu-iPSMA (
Lu-prostate specific membrane antigen inhibitor),
Ac-iPSMA and
RaCl
to prostate cancer cell nuclei in a simplified ...model of bone by using an experimental in-vitro prostate cancer LNCaP cell biokinetic study and Monte Carlo simulation with the MCNPX code. Results showed that
Ac-iPSMA releases a nine hundred-fold radiation dose greater than
Lu-iPSMA and 14 times more than
RaCl
per unit of activity retained in bone.
Ac-iPSMA could be the best option for treatment of bone metastases in prostate cancer.
SPECT/CT images in patients have demonstrated the ability of
99m
TcTc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (
99m
TcTc-iPSMA) to detect tumors and metastases of prostate cancer. Considering that theranostics ...combines the potential of therapeutic and diagnostic radionuclides in the same molecular probe, the aim of this research was to estimate the biokinetics and dosimetry of
177
Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu (
177
Lu-iPSMA) in healthy subjects and analyze the response in patients receiving
177
Lu-iPSMA therapeutic doses.
177
Lu-iPSMA was obtained from lyophilized formulations with radiochemical purities >98%. Whole-body images from five healthy subjects were acquired at 20 min, 6, 24, 48, and 120 h after
177
Lu-iPSMA administration (185 MBq). The image sequence was used to extrapolate the
177
Lu-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (
N
) that occurred in the source regions.
N
data were the input for the OLINDA/EXM code to calculate internal radiation doses. Ten patients (median age: 68 y; range 58–86 y) received from 1 to 4 cycles of
177
Lu-iPSMA (3.7 or 7.4 GBq) every 8–10 weeks. Response was evaluated using the
68
Ga-PSMA-ligand-PET/CT or
99m
Tc-iPSMA-SPECT/CT diagnostic images and serum PSA levels before and after
177
Lu-iPSMA treatment. The blood activity showed a half-life value of 1.1 h for the fast component (
T
1/2
α
= ln2/0.614), 9.2 h for the first slow component (
T
1/2
β
= ln2/0.075), and 79.6 h for the second slow component (
T
1/2
γ
= ln2/0.008). The average absorbed doses were 0.23, 0.28, 0.88, and 1.17 Gy/GBq for the spleen, liver, kidney, and salivary glands. A total of 18 cycles were performed in 10 patients. A PSA decrease and some reduction of the radiotracer uptake (SUV) in tumor lesions occurred in 60% and 70% of the patients, respectively.
177
Lu-iPSMA obtained from kit formulations showed high tumor uptake with good response rates in patients. The results obtained in this study warrant further clinical studies to establish the optimal number of treatment cycles and for evaluating the effect of this therapeutic agent on survival of patients.
The aim of this work was to synthesize Lys1(α,γ-Folate)-Lys3(177Lu-DOTA)-Bombesin (1-14) (177Lu-Folate-BN), as well as to assess its potential for molecular imaging and targeted radiotherapy of ...breast tumors expressing folate receptors (FR) and gastrin-releasing peptide receptors (GRPR). Radiation absorbed doses of 177Lu-Folate-BN (74 MBq, i.v.) estimated in athymic mice with T47D-induced breast tumors (positive to FR and GRPR), showed tumor doses of 23.9±2.1Gy. T47D-tumors were clearly visible (Micro-SPECT/CT images). 177Lu-Folate-BN demonstrated properties suitable as a theranostic radiopharmaceutical.
•177Lu-Folate-BN improves recognition of breast cancer cells positive to FR and GRPR.•177Lu-Folate-BN shows theranostic (imaging and radiation therapy) properties.•The heterobivalent 177Lu-Folate-BN tracer interacts with different targets on tumors.
SPECT/CT images in patients have demonstrated the ability of 99mTcTc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (99mTcTc-iPSMA) to detect tumors and metastases of prostate cancer. Considering that theranostics ...combines the potential of therapeutic and diagnostic radionuclides in the same molecular probe, the aim of this research was to estimate the biokinetics and dosimetry of 177Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu (177Lu-iPSMA) in healthy subjects and analyze the response in patients receiving 177Lu-iPSMA therapeutic doses. 177Lu-iPSMA was obtained from lyophilized formulations with radiochemical purities >98%. Whole-body images from five healthy subjects were acquired at 20 min, 6, 24, 48, and 120 h after 177Lu-iPSMA administration (185 MBq). The image sequence was used to extrapolate the 177Lu-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. Ten patients (median age: 68 y; range 58–86 y) received from 1 to 4 cycles of 177Lu-iPSMA (3.7 or 7.4 GBq) every 8–10 weeks. Response was evaluated using the 68Ga-PSMA-ligand-PET/CT or 99mTc-iPSMA-SPECT/CT diagnostic images and serum PSA levels before and after 177Lu-iPSMA treatment. The blood activity showed a half-life value of 1.1 h for the fast component (T1/2α = ln2/0.614), 9.2 h for the first slow component (T1/2β = ln2/0.075), and 79.6 h for the second slow component (T1/2γ = ln2/0.008). The average absorbed doses were 0.23, 0.28, 0.88, and 1.17 Gy/GBq for the spleen, liver, kidney, and salivary glands. A total of 18 cycles were performed in 10 patients. A PSA decrease and some reduction of the radiotracer uptake (SUV) in tumor lesions occurred in 60% and 70% of the patients, respectively. 177Lu-iPSMA obtained from kit formulations showed high tumor uptake with good response rates in patients. The results obtained in this study warrant further clinical studies to establish the optimal number of treatment cycles and for evaluating the effect of this therapeutic agent on survival of patients.
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 177-AuNP-cRGDfK(C), the MCF7 cell proliferation was significantly inhibited.
SPECT/CT images in patients have demonstrated the ability of
TcTc-EDDA/HYNIC-Lys(Nal)-Urea-Glu (
TcTc-iPSMA) to detect tumors and metastases of prostate cancer. Considering that theranostics ...combines the potential of therapeutic and diagnostic radionuclides in the same molecular probe, the aim of this research was to estimate the biokinetics and dosimetry of
Lu-DOTA-HYNIC-Lys(Nal)-Urea-Glu (
Lu-iPSMA) in healthy subjects and analyze the response in patients receiving
Lu-iPSMA therapeutic doses.
Lu-iPSMA was obtained from lyophilized formulations with radiochemical purities >98%. Whole-body images from five healthy subjects were acquired at 20 min, 6, 24, 48, and 120 h after
Lu-iPSMA administration (185 MBq). The image sequence was used to extrapolate the
Lu-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (
) that occurred in the source regions.
data were the input for the OLINDA/EXM code to calculate internal radiation doses. Ten patients (median age: 68 y; range 58-86 y) received from 1 to 4 cycles of
Lu-iPSMA (3.7 or 7.4 GBq) every 8-10 weeks. Response was evaluated using the
Ga-PSMA-ligand-PET/CT or
Tc-iPSMA-SPECT/CT diagnostic images and serum PSA levels before and after
Lu-iPSMA treatment. The blood activity showed a half-life value of 1.1 h for the fast component (
= ln2/0.614), 9.2 h for the first slow component (
= ln2/0.075), and 79.6 h for the second slow component (
= ln2/0.008). The average absorbed doses were 0.23, 0.28, 0.88, and 1.17 Gy/GBq for the spleen, liver, kidney, and salivary glands. A total of 18 cycles were performed in 10 patients. A PSA decrease and some reduction of the radiotracer uptake (SUV) in tumor lesions occurred in 60% and 70% of the patients, respectively.
Lu-iPSMA obtained from kit formulations showed high tumor uptake with good response rates in patients. The results obtained in this study warrant further clinical studies to establish the optimal number of treatment cycles and for evaluating the effect of this therapeutic agent on survival of patients.
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