The Distribution and Imaging of 99mTc-nGO-PEG-FA in Human Patu8988 Tumor-Bearing Nude Mice.

Background: To study the distribution and imaging of 99mTc-nGO-PEG-FA in human pancreatic cancer Patu8988 tumor-bearing nude mice, and to explore its usefulness as an imaging reagent for pancreatic cancer. Materials and Methods: Natural graphite powder was used as raw material to prepare the nanosized graphene oxide (nGO) by using the modified Hummers method, and then was covalently modified by polyethylene glycol (PEG) on the surface of nGO. The nGO was further optimized by in vitro cell experiment, and then conjugated with the targeting molecule folic acid (FA) to form nGO-PEG-FA system. The nGO-PEG-FA was finally labeled by radioactive nuclide 99mTc by direct labeling method to form the 99mTc-nGO-PEG-FA molecular imaging probe. Nude mice bearing patu8988 pancreatic cancer xenografts were intravenous injection (I.V.) injected with 99mTc-nGO-PEG-FA, and the distribution of 99mTc-nGO-PEG-FA in nude mice at different time course was investigated by determination of tissue uptake of radioactivity (%ID/g), as well as the single photon emission computed tomography (SPECT) imaging at different time course. Results: The labeling rate of nGO-PEG-FA with 99mTc was (90.08 ± 2.34)%, and the highest binding rate of 99mTc-nGO-PEG-FA with Patu8988 cells was (3.15 ± 0.31)%. The radioactive uptake in tumor reached (5.11 ± 1.23)%ID/g at 6 h after I.V. injection of 99mTc-nGO-PEG-FA in nude mice. Meanwhile, the radioactive uptake in liver, spleen, and lung was also high and reached (10.33 ± 1.22)%ID/g, (5.86 ± 0.59)%ID/g, and (3.55 ± 0.93)%ID/g, respectively, whereas less radioactivity uptake was observed in the heart (1.12 ± 0.33)%ID/g and blood (2.76 ± 0.39)%ID/g, respectively. The tumors can be clearly imaged at 4.0-6.0 h after 99mTc-nGO-PEG-FA injection. Conclusions: 99mTc-nGO-PEG-FA can efficiently target pancreatic cancer, which may be developed as an imaging agent for pancreatic cancer.

The effect of lentiviral vector-mediated RNA interference targeting hypoxia-inducible factor 1α on the uptake of fluorodeoxyglucose ((18)f) in the human pancreatic cancer cell line, patu8988.

Hypoxia can stimulate (18)F-fluorodeoxyglucose ((18)F-FDG) uptake in cultured tumor cells. This study has investigated the effect of lentiviral vector-mediated RNA interference (RNAi) targeting hypoxia-inducible factor 1α (HIF-1α) on the changes in HIF-1 and glucose transporter 1 (Glut-1) expression, the cell growth, and the uptake of (18)F-FDG in the human pancreatic cancer cell line, Patu8988. Lentiviral RNAi vector targeting the HIF-1α gene (LV-HIF-1αRNAi) was constructed and used to treat cells at various concentrations (25-200 nM). The expression changes of HIF-1α and Glut-1 in hypoxic Patu8988 cells after RNAi treatment were determined using real time reverse transcription-polymerase chain reaction (real-time PCR). The inhibition rate of cell proliferation 48 hours after the addition of 10 µL of different concentrations of LV-HIF-1αRNAi (25-200 nM) was assayed using the MTT method. Meanwhile, the cell uptake of (18)F-FDG was also assessed. After RNAi transfection, the relative expression levels of HIF-1α mRNA and Glut-1 under hypoxia were reduced and the relative expression levels of HIF-1α protein also decreased. Compared with the control group, the inhibition rates of cell proliferation under different viral dosages were 5.98%, 15.65%, 26.42%, and 40.81%, respectively, positively correlated with the viral doses (r=0.558, p<0.05). Under hypoxia, Glut-1 mRNA expression in Patu8988 cells treated with 200 nM of LV-HIF-1αRNAi for 24, 48, and 72 hours, respectively, was positively correlated with the inhibition rate of cell proliferation (r=0.618, p<0.05) as well as the inhibition rate of (18)F-FDG uptake (r=0.664, p<0.05), while the latter two displayed a positive correlation with each other too (r=0.582, p<0.05). Under hypoxia, RNAi targeting HIF-1α significantly inhibited the expression of Glut-1 mRNA in Patu8988 pancreatic cancer cells and their uptake of (18)F-FDG. These results suggest that LV-HIF-1αRNAi may form a new treatment for pancreatic cancer, and the effectiveness of the treatment can be readily assessed with (18)F-FDG imaging.

Equilibrium radionuclide angiocardiography for the evaluation of right ventricular ejection fraction in patients with cardiac disorders.

OBJECTIVE: To compare correlation between right ventricular ejection fraction (RVEF) derived from MRI and equilibrium radionuclide angiocardiography (ERNA) depicted from the left anterior oblique (LAO) view and anterior (ANT) view [designated as ERNA (LAO) and ERNA (ANT), respectively]. METHODS: Twenty-one patients with cardiac disorders received ERNA and cardiac MRI examination within 2 weeks were enrolled in this study. The region of interest (ROI) in right ventricle was depicted from the LAO and anterior (ANT) views to calculate the ERNA (LAO) and ERNA (ANT). Cardiac MRI was performed as served as reference standard to compare correlation between RVEF derived from MRI and ERNA (LAO)/ERNA (ANT), respectively. The repeatability was evaluated according to the intraclass correlation coefficient (ICC). RESULTS: RVEF obtained through MRI was closely correlated with that obtained through ERNA (LAO) view (r=0.883) and ERNA (ANT) view (r=0.891), respectively. Bland-Altam analysis indicated the RVEF derived from the ERNA (LAO) view was obviously underestimated in patients with right ventricular enlargement. Meanwhile, the RVEF derived from the anterior view was much closer to the RVEF derived from MRI compared with that obtained from the LAO view. CONCLUSIONS: ERNA is effective for the determination of RVEF. LAO is still preferred for the determination of RVEF, but the RVEF may be underestimated in the patients with right ventricular enlargement. Determination of RVEF based on ANT is solely recommended in the determination of RVEF in patients with right ventricular enlargement and serves as a control.

Antitumor effects of 32P-chromic-poly (L-lactide) brachytherapy in nude mice with human prostate cancer.

The aim of the present study was to investigate the antitumor effects and tissue distribution of 32P-chromic-poly (L-lactide) (32P-CP-PLLA) in nude mice with human prostate cancer. Tumor models were obtained by transplantation of PC-3M tumor cells into male BALB/c nude mice. Animals were randomly divided into control, 32P-chromic phosphate (32P-CP) colloid and 32P-CP-PLLA groups (all n=20). A series of indices were investigated, including apoptosis of tumor cells, rate of apoptosis, expression of caspase 3 and 8, biodistribution and intratumoral concentration of 32P-CP-PLLA, intensity of radioactivity, tumor volume and microvessel density (MVD). Highly concentrated radioactivity of 32P-CP-PLLA in the tumor mass was detected by single photon emission computed tomography (SPECT) scanning. The residual activities of the 32P-CP-PLLA and 32P-CP colloid groups were 3.02±0.32 and 1.76±0.31 MBq, respectively, on day 14 following treatment. The tumor inhibition rates were 67.24±3.55 and 55.92±7.65%, respectively (P<0.01). Necrotic changes, in conjunction with apoptosis, were observed in the treatment group. MVD values for the 32P-CP-PLLA and 32P-CP colloid groups were 28.24±10.07 and 36.15±11.06, respectively. 32P-CP-PLLA showed an excellent capacity for killing tumor cells, inducing apoptosis and inhibiting angiogenesis.

Preliminary study of the biodegradation and the correlation between in vitro and in vivo release of (32)P-chromic phosphate-poly(L-lactide) seeds.

OBJECTIVE: To investigate the drug release kinetic of (32)P-chromic phosphate-poly(L-lactide) ((32)P-CP-PLLA). METHODS: (32)P-CP-PLLA were placed into physiological saline and H22 solid tumor mass, respectively. The weight loss rate and radioactivity release rate were evaluated. The release of the microparticles was evaluated using fitting curves. The correlation of the release of the microparticles between physiological saline and H22 solid tumor mass was analyzed. RESULTS: Close correlation was noted in the release of the microparticles between physiological saline and H22 solid tumor mass. The Weibull equation showed the best fitting of (32)P-CP-PLLA in physiological saline. CONCLUSIONS: The Weibull equation could be used for the predictive release of microparticles in vitro. The parameters obtained from the drug release kinetics could be used to estimate the dose of radiopharmaceuticals within the tumors and the surrounding tissues.