Biomedical subjects

Songji Zhao

Publications and source records attributed to Songji Zhao.

9 recordsLinked to original sources

PubMed2005

Evaluating performance of a pixel array semiconductor SPECT system for small animal imaging.

OBJECTIVES: Small animal imaging has recently been focused on basic nuclear medicine. We have designed and built a small animal SPECT imaging system using a semiconductor camera and a newly designed collimator. We assess the performance of this system for small object imaging. METHODS: We employed an MGC 1500 (Acrorad Co.) camera including a CdTe semiconductor. The pixel size was 1.4 mm/pixel. We designed and produced a parallel-hole collimator with 20-mm hole length. Our SPECT system consisted of a semiconductor camera with the subject holder set on an electric rotating stage controlled by a computer. We compared this system with a conventional small animal SPECT system comprising a SPECT-2000H scanner with four Anger type cameras and pinhole collimators. The count rate linearity for estimation of the scatter was evaluated for a pie-chart phantom containing different concentrations of 99mTc. We measured the FWHM of the 99mTc SPECT line source along with scatter. The system volume sensitivity was examined using a flood source phantom which was 35 mm long with a 32-mm inside diameter. Additionally, an in vivo myocardial perfusion SPECT study was performed with a rat. RESULTS: With regards to energy resolution, the semiconductor camera (5.6%) was superior to the conventional Anger type camera (9.8%). In the count rate linearity evaluation, the regression lines of the SPECT values were y = 0.019x + 0.031 (r2 = 0.999) for our system and y = 0.018x + 0.060 (r2 = 0.997) for the conventional system. Thus, the scatter count using the semiconductor camera was less than that using the conventional camera. FWHMs of our system and the conventional system were 2.9 +/- 0.1 and 2.0 +/- 0.1 mm, respectively. Moreover, the system volume sensitivity of our system [0.51 kcps/(MBq/ ml)/cm] was superior to that of the conventional system [0.44 kcps/(MBq/ml)/cm]. Our system provided clear images of the rat myocardium, sufficient for practical use in small animal imaging. CONCLUSIONS: Our SPECT system, utilizing a semiconductor camera, permits high quantitative analysis by virtue of its low scatter radiation and high sensitivity. Therefore, this system may contribute to molecular imaging of small animals and basic medical research.

Animals↗

PubMed2005

Biologic correlates of intratumoral heterogeneity in 18F-FDG distribution with regional expression of glucose transporters and hexokinase-II in experimental tumor.

UNLABELLED: The biologic mechanisms involved in the intratumoral heterogeneous distribution of 18F-FDG have not been fully investigated. To clarify factors inducing heterogeneous 18F-FDG distribution, we determined the intratumoral distribution of 18F-FDG by autoradiography (ARG) and compared it with the regional expression levels of glucose transporters Glut-1 and Glut-3 and hexokinase-II (HK-II) in a rat model of malignant tumor. METHODS: Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle (n = 7). Tumor tissues were excised 1 h after the intravenous injection of 18F-FDG and sectioned to obtain 2 adjacent slices for ARG and histochemical studies. The regions of interest (ROIs) were placed on ARG images to cover mainly the central (CT) and peripheral (PT) regions of viable tumor tissues and necrotic/apoptotic (NA) regions. The radioactivity in each ROI was analyzed quantitatively using a computerized imaging analysis system. The expression levels of Glut-1, Glut-3, and HK-II were determined by immunostaining and semiquantitative evaluation. The hypoxia-inducible factor 1 (HIF-1) was also immunostained. RESULTS: ARG images showed that intratumoral 18F-FDG distribution was heterogeneous. The accumulation of 18F-FDG in the CT region was the highest, which was 1.6 and 2.3 times higher than those in the PT and NA regions, respectively (P < 0.001). The expression levels of Glut-1, Glut-3, and HK-II were markedly higher in the CT region (P < 0.001) compared with those in the PT region. The intratumoral distribution of 18F-FDG significantly correlated with the expression levels of Glut-1, Glut-3, and HK-II (r = 0.923, P < 0.001 for Glut-1; r = 0.829, P < 0.001 for Glut-3; and r = 0.764, P < 0.01 for HK-II). The positive staining of HIF-1 was observed in the CT region. CONCLUSION: These results demonstrate that intratumoral 18F-FDG distribution corresponds well to the expression levels of Glut-1, Glut-3, and HK-II. The elevated expression levels of Glut-1, Glut-3, and HK-II, induced by hypoxia (HIF-1), may be contributing factors to the higher 18F-FDG accumulation in the CT region.

Animals↗

PubMed2005

Enhanced apoptotic reaction correlates with suppressed tumor glucose utilization after cytotoxic chemotherapy: use of 99mTc-Annexin V, 18F-FDG, and histologic evaluation.

UNLABELLED: Cancer chemotherapy enhances the apoptosis, whereas apoptosis is a suicidal mechanism requiring energy. We determined the relationship between apoptosis and glucose utilization during cancer chemotherapy using (99m)Tc-annexin V ((99m)Tc-annexin A5) and (18)F-FDG and compared their uptake with histologic findings in a rat tumor model. METHODS: Allogenic hepatoma cells (KDH-8) were inoculated into the left calf muscle of male Wistar rats (WKA). Eleven days after the inoculation, the rats were randomly divided into 3 groups: The first group (n = 7) received a single dose of gemcitabine (90 mg/kg, intravenously), the second group (n = 8) received cyclophosphamide (150 mg/kg, intraperitoneally), and the third group (n = 7) was untreated and served as the control group. We injected (99m)Tc-annexin V 48 h after the chemotherapy and then injected (18)F-FDG to all rats 1 h before sacrifice. Six hours after (99m)Tc-annexin V injection, the rats were sacrificed and the organs, including the tumor, were removed and radioactivity was counted. The radioactivities of (18)F and (99m)Tc in the organs were determined using normalization by tissue weight. Histologic evaluation by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method and the immunostaining of glucose transporter-1 (GLUT-1) were also performed to obtain the indices of apoptosis and glucose utilization, respectively. The rate of positively stained cells was calculated and analyzed statistically. RESULTS: After chemotherapy using gemcitabine and cyclophosphamide, the (99m)Tc-annexin V uptake (percentage injected dose per gram x kg [(%ID/g) x kg]; mean +/- SD) in tumor increased significantly (0.062 +/- 0.012 (%ID/g) x kg in the gemcitabine-treated group and 0.050 +/- 0.012 (%ID/g) x kg in the cyclophosphamide group vs. 0.031 +/- 0.005 (%ID/g) x kg in the control group; P < 0.01). In contrast, the (18)F-FDG in tumor decreased significantly (0.483 +/- 0.118 (%ID/g) x kg in the gemcitabine group and 0.583 +/- 0.142 (%ID/g) x kg in the cyclophosphamide group) compared with that in the control group (0.743 +/- 0.084 (%ID/g) x kg; P < 0.01). In addition, (18)F-FDG uptake in tumor negatively correlated with (99m)Tc-annexin V uptake (r = -0.75; P < 0.01). In the gemcitabine and cyclophosphamide groups, the rate of TUNEL positively stained cells was significantly higher than that in the control group (10.2% +/- 1.7% and 8.0% +/- 1.5% vs. 5.2% +/- 1.5%; P < 0.01), whereas the GLUT-1 expression level showed no definite changes in histologic analyses. CONCLUSION: These data indicate that an enhanced apoptotic reaction correlated with suppressed tumor glucose utilization after cytotoxic chemotherapy as determined using radiotracers and histologic evaluation. The increase in (99m)Tc-annexin V and the decrease in (18)F-FDG in tumor can be useful markers for predicting therapeutic outcomes and for prognosis at the early stage of chemotherapy.

Animals↗

PubMed2004

18F-FDG PET is superior to 67Ga SPECT in the staging of non-Hodgkin's lymphoma.

OBJECTIVE: Our study aims to compare diagnostic accuracy between 18F-FDG PET and 67Ga SPECT in the staging of non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with non-Hodgkin's lymphoma, underwent 18F-FDG PET, 67Ga SPECT and CT for the pretreatment staging of malignant lymphoma between August 1999 and March 2002. 18F-FDG PET imaging was obtained 60 minutes after the intravenous administration of 185 MBq of 18F-FDG. 67Ga SPECT imaging was obtained 2 days after the intravenous administration of 148 MBq of 67Ga. 18F-FDG PET and 67Ga SPECT were performed within one month. Both imagings were performed on the area from the neck to the pelvis. The 18F-FDG PET and 67Ga SPECT findings were compared with the CT findings and the clinical course. RESULTS: Sixty-six nodal lesions were clinically confirmed. Of these, 32 were identified by both 18F-FDG PET and 67Ga SPECT. The remaining 34 lesions were identified only by 18F-FDG PET. The mean (+/- SD) sizes' of the nodes were 34.7 +/- 32.4 mm for 18F-FDG-positive and 67Ga-positive lesions and 15.7 +/- 8.3 mm for 18F-FDG-positive and 67Ga-negative lesions (p < 0.001). Of the 23 extranodal lesions, 12 were identified by both 18F-FDG PET and 67Ga SPECT, whereas 6 lesions were identified by only 18F-FDG PET. Five lesions were not identified by either technique. No 18F-FDG-negative but 67Ga-positive nodal or extranodal lesions were observed. The difference in findings between the two studies is related to the difference in the size but not in the histology or site of the lesions. CONCLUSION: 18F-FDG PET detected significantly more lesions particularly small lesions than 67Ga SPECT. Thus, 18F-FDG PET is considered to be superior to 67Ga SPECT in the staging of non-Hodgkin' s lymphoma.

Citrates↗

PubMed2004

Gastrointestinal uptake of FDG after N-butylscopolamine or omeprazole treatment in the rat.

OBJECTIVE: Gastrointestinal (GI) uptake of 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) is frequently observed in whole-body positron emission tomography (PET) images. Such physiological uptake may interfere with accurate interpretation. The aim of the present study was to determine whether physiological gastrointestinal FDG uptake can be decreased by means of an antiperistaltic agent, N-butylscopolamine, or a gastric secretion inhibitor, omeprazole. METHODS: Sprague-Dawley rats were divided into three groups: omeprazole-treated (n = 6), N-butylscopolamine-treated (n = 7), and control group (n = 6). The rats in the omeprazole-treated group were administered omeprazole (1.0 mg/kg) intravenously 45 minutes before FDG injection. The rats in the N-butylscopolamine-treated group were administered N-butylscopolamine (1.0 mg/kg) intramuscularly 10 minutes before FDG injection. Sixty minutes after FDG injection under overnight fasting state, the gastrointestinal tissues were excised and weighed to determine the radioactivity of 18F using a gamma counter. RESULTS: The mean values of FDG uptake in the esophagus, stomach, small intestine, cecum and colon of the N-butylscopolamine-treated group vs. the omeprazole-treated group were 148% vs. 162%, 109% vs. 113%, 113% vs. 88%, 102% vs. 85%, 105% vs. 70% of the control group, respectively. There were no statistical differences in FDG uptake rate in the esophagus, stomach, or cecum among the three groups. FDG uptake rates in the small intestine and colon of the omeprazole-treated group were significantly lower than those in the control group. CONCLUSION: Physiological FDG uptake in the GI tract was not decreased by the administration of N-butylscopolamine. Omeprazole was effective in decreasing FDG uptake in the small intestine and colon. Omeprazole has a potential to decrease FDG uptake rate in a limited part of the GI tract.

Animals↗

PubMed2004

Feasibility of 99mTc-annexin V for repetitive detection of apoptotic tumor response to chemotherapy: an experimental study using a rat tumor model.

UNLABELLED: Annexin V (annexin A5), a human protein with a high affinity for phosphatidylserine, labeled with (99m)Tc can detect apoptosis in vivo. In the repetitive detection of apoptosis with (99m)Tc-annexin V, however, the specific binding of annexin V to phosphatidylserine might affect the subsequent detection of apoptosis with this compound. To determine whether there is interference with repetitive doses of annexin V, we evaluated the effects of previous administration of cold annexin V on accumulation of (99m)Tc-annexin V in tumors in an experimental tumor model. METHODS: Rats bearing hepatoma received cyclophosphamide (150 mg/kg, intraperitoneally) 11 d after the tumor inoculation. Cold annexin V (20 microg/kg, intravenously) was administered 24 h before or after the cyclophosphamide treatment (n = 7/group). (99m)Tc-Annexin V was injected intravenously (radioactive dose, 5-23 MBq/kg; mass dose, 20 microg/kg), and radioactivity in tissues was determined 6 h later. RESULTS: Accumulation of (99m)Tc-annexin V in tumors was not significantly affected by previous treatment with cold annexin V before or after chemotherapy. CONCLUSION: These results demonstrate the feasibility of (99m)Tc-annexin V imaging for repetitive detection of apoptosis, which is highly required in the clinical setting.

Animals↗

PubMed2004

Time course of apoptotic tumor response after a single dose of chemotherapy: comparison with 99mTc-annexin V uptake and histologic findings in an experimental model.

UNLABELLED: In tumors the process of apoptosis occurs over an interval of time after chemotherapy. To determine the best timing for detecting apoptosis in vivo with (99m)Tc-annexin V after chemotherapy, we examined the changes in (99m)Tc-annexin V accumulation over time in comparison with those of caspase-3 and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) expression level after cyclophosphamide treatment in an experimental model. METHODS: Hydrazinonicotinamide (HYNIC)-annexin V was labeled with (99m)Tc ((99m)Tc-annexin V). Rats were inoculated with allogenic hepatoma cells (KDH-8) into the left calf muscle. Eleven days after the inoculation, the rats were randomly divided into the group receiving a single dose of cyclophosphamide (150 mg/kg intraperitoneally) and the control group. (99m)Tc-Annexin V (18.5 MBq [0.5 mCi] per rat) was injected intravenously in the rats 4, 12, and 20 h after the treatment and also to the control rats (n = 5 in each group). Radioactivity in tissues was determined 6 h after (99m)Tc-annexin V injection. Immunostaining of caspase-3 and TUNEL were performed to detect apoptosis, and the rates of positively stained cells were calculated. RESULTS: (99m)Tc-Annexin V accumulation in tumors significantly increased at 20 h (0.077 +/- 0.007 [%ID/g] x kg, where %ID/g = percentage injected dose per gram) but not at 4 or 12 h (0.048 +/- 0.008 and 0.052 +/- 0.014 [%ID/g] x kg, respectively) after cyclophosphamide treatment. (99m)Tc-Annexin V accumulation in tumors and the rate of apoptotic cells determined by caspase-3 immunostaining and TUNEL were significantly higher in treated rats 20 h after cyclophosphamide treatment as compared with control rats. CONCLUSION: The effective detection of apoptotic tumor response with (99m)Tc-annexin V required 20 h after cyclophosphamide treatment in an experimental model. The present results provide an important basis for determining the best timing of annexin V imaging after the start of chemotherapy in a clinical setting.

Animals↗

PubMed2003

Dominant-negative hypoxia-inducible factor-1 alpha reduces tumorigenicity of pancreatic cancer cells through the suppression of glucose metabolism.

In the tumor cells exposed to hypoxia, hypoxia-inducible factor-1 (HIF-1)-mediated adaptation responses such as angiogenesis and anaerobic metabolism are induced for their survival. We have recently reported that the constitutive expression of HIF-1 alpha renders pancreatic cancer cells resistant to apoptosis induced by hypoxia and glucose deprivation. We then established dominant-negative HIF-1 alpha (dnHIF-1 alpha) transfectants and examined their susceptibility to apoptosis and growth inhibition induced by hypoxia and glucose deprivation in vitro and their tumorigenicity in SCID mice. We further examined the expressions of aldolase A and Glut-1 in vitro and Glut-1 expression and glucose uptake in the tumor tissues and microvessel counts in the tumor tissues. As a result, dnHIF-1 alpha rendered the pancreatic cancer cells sensitive to apoptosis and growth inhibition induced by hypoxia and glucose deprivation. Also it abrogated the enhanced expression of Glut-1 and aldolase A mRNAs under hypoxia and reduced the expression of Glut-1 and the glucose uptake in the tumor tissues and consequently in vivo tumorigenicity. We found no significant difference in the microvessel counts among the tumor tissues. From these results, we suggest that the disruption of the HIF-1 pathway might be effective in the treatment of pancreatic cancers.

Adenocarcinoma↗

PubMed2003

Detection of apoptotic tumor response in vivo after a single dose of chemotherapy with 99mTc-annexin V.

UNLABELLED: Annexin V, a human protein with a high affinity for phosphatidylserine, has been labeled with (99m)Tc to detect apoptosis in vivo. To determine the effectiveness of imaging with this agent as a reflection of the degree of apoptosis after the first dose of chemotherapy, we studied rats with an engrafted hepatoma. METHODS: Annexin V was labeled with (99m)Tc (specific activity, 3.0 MBq/ micro g protein). Eleven days after being inoculated with allogenic hepatoma cells (KDH-8) in the left calf muscle, the rats were randomized to receive a single dose of cyclophosphamide (150 mg/kg intraperitoneally) or to serve as controls. (99m)Tc-annexin V was injected 20 h later. Radioactivity in tissues was determined 6 h after injection of (99m)Tc-annexin V. Tumor uptake of (14)C-iodoanitpyrine was determined as a marker of tumor blood flow. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) of tissue harvested at necropsy was performed to detect apoptosis in the tumor. RESULTS: Cyclophosphamide treatment significantly increased the tumor uptake (percentage activity of injected dose per gram of tissue after normalization to the animal's weight [%ID/g/kg]) of (99m)Tc-annexin V (0.070 +/- 0.007 %ID/g/kg for treated rats and 0.046 +/- 0.009 %ID/g/kg for controls, P < 0.001). (14)C-iodoantipyrine uptake was similar in the treated and untreated groups. The number of TUNEL-positive cells in the tumor was significantly larger in the treated rats (297.70 +/- 50.34 cells/mm(2)) than in the control rats (168.45 +/- 23.60 cells/mm(2), P < 0.001). Tumor uptake of (99m)Tc-annexin V correlated with the number of TUNEL-positive cells in the tumor (r = 0.712; P < 0.001). CONCLUSION: Tumor uptake of (99m)Tc-annexin V was significantly increased by a single dose of cyclophosphamide treatment, and the increase was concordant with the number of TUNEL-positive cells in the tumor. The current results are suggestive of the utility of (99m)Tc-annexin V as a noninvasive means to assess tumor response, although further testing, including clinical evaluation, is required.

Animals↗