Relationship between fluorodeoxyglucose uptake and overexpression of glucose transport protein 1 and hexokinase-Ⅱ in early-stage nasopharyngeal carcinoma / 中华核医学杂志

Objective To discuss the molecular mechanism of 18F-fluorodeoxyglucose (FDG) uptake in tumor and to assess its value to identify pathologic type and cancer staging in patients with earlystage nasopharyngeal carcinoma.Methods Forty patients with nasopharyngeal carcinoma of early-stage,including 12 cases with T1 stage and 28 cases with T2 stage, underwent FDG PET imaging.The maximum standardized uptake value ( SUVmax ) and mean standardized uptake value ( SUVmean ) of FDG uptake of each patient were measured and compared between T1 and T2 stage by t-test.The expression of glucose transport protein 1 ( Glut1 ) and hexokinase- Ⅱ ( HK- Ⅱ ) of each case was measured in paraffin sections by streptavidin-perosidase (SP) immunohistochemistry.The positive expression rate of Glut1 and HK- Ⅱ was calculated and compared between T1 and T2 by x2 test.Meanwhile, the correlation between the expression of Glut1 or HK-Ⅱ and the SUVmax was tested by Pearson analysis.Results The SUVmax and SUVmean in 40 patients were 9.45 ± 1.87 and 6.04 ± 1.09, respectively.The SUVmax of patients with T1 stage (8.95 ± 1.91 ) was significantly lower (t =4.46, P＜0.001 ) than that of patients with T2 stage (11.55 ± 1.70), and the SUVmean of patients with T1 stage (5.61 ± 1.08) was significantly lower ( t = 6.76, P ＜ 0.001 ) than that of patients with T2 stage (7.98 ± 1.10) too.Among 40 patients, all patients showed positive expression of Glut1 and HK-Ⅱ , and the positive expression rate of Glut1 and HK-Ⅱ was ( 45.2 ± 10.9 )% and ( 68.3 ±9.5)%, respectively.The positive expression rate of Glut1 was (38.4 ±8.1)% in T1 stage and (49.7 ±12.6)% in T2 stage, which displayed no difference (x2 =40.58, P＞0.05), but the HK-Ⅱ positive expression rate showed significant difference (x2 =58.71, P＜0.05) between T1 stage (60.1 ±11.1)% and T2 stage (77.9 ± 14.7 )%.The correlation analysis indicated that there was low-degree positive correlation (r =0.369, P=0.019) between the SUVmax and Glut1 expression, and there was medium-degree positive correlation (r = 0.549, P = 0.001 ) between the SUVmax and HK-Ⅱ expression.Conclusion Expression of Glut1 and HK-Ⅱ was positively correlated with FDG uptake in patients with early-stage nasopharyngeal carcinoma.

In vivo and in vitro stability of ¹³¹I-Herceptin and its form of existence in the blood of rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the in vivo and in vitro stability of (131)I-Herceptin and its form of existence in the blood.</p><p><b>METHODS</b>Herceptin was labelled with iodine-131 using the Iodogen method. (131)I-Herceptin was stored at 4 degrees celsius for 3, 24, 48, 72 and 96 h, and the radiochemical purity (RCP) was measured by high performance liquid chromatography (HPLC). Five rabbits received injections of (131)I-Herceptin and at 1, 3, 6, 24, 48, 72, 96 and 120 h after the injection, blood samples were taken to measure the RCP of (131)I-Herceptin in the serum, and the radio count of the serum and blood cells was calculated.</p><p><b>RESULTS</b>The baseline RCP of (131)I-Herceptin was (94.9±2.7)%. The RCP was stable after placement at 4 degrees celsius for not over 72 h (F=15.985, P<0.001), but was significantly lowered to (82.6±2.8)% after preservation for over 72 h (t=9.971, P<0.001). Within the time of 1.0 to 96 h after injection in rabbits, (131)I-Herceptin existed mainly in the serum with a radio count of 81%-87%; 24 h after the injection, the RCP of (131)I-Herceptin in the serum was significantly lowered to (75.4±3.9)% (t=6.564, P<0.001).</p><p><b>CONCLUSION</b>Storage at 4 degrees celsius for no more than 72 h does not obviously affect the activity of (131)I-Herceptin in terms of RCP. After injection in rabbits, (131)I-Herceptin exists mainly in the serum and its radiochemical purity remains stable within 24 h, after which obvious degradation occurs.</p>

Analysis of radioactive distribution in the sacrum in whole-body bone scanning / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the radiogenic distribution in the sacrum in whole-body bone scanning.</p><p><b>METHODS</b>A total of 212 patients receiving whole-body bone scanning without any explicit bone metastases were divided into different age and gender groups. The radioactive distribution in the sacrum in whole-body bone scanning was analyzed statistically.</p><p><b>RESULTS</b>Of these cases, 31.1% presented with thin radioactive distribution in the sacrum and 11.3% exhibited increased radioactive distribution. Normal radioactive distribution in the sacrum was found in 57.6% of the cases. In both male and female elderly patients (>70 years), the rate of normal radioactive distribution in the sacrum was obviously reduced with increased rate of thin radioactive distribution. The female elderly patients showed higher rate of increased radioactive distribution in the sacrum than male elderly patients.</p><p><b>CONCLUSION</b>The radioactive distribution in the sacrum is similar between female and male patients. Elderly male patients over 70 years have generally thin radioactive distribution in the sacrum due to the presence of osteoporosis, which is also associated with latent fracture of the sacrum to result in increased radioactive distribution in the sacrum in whole-body bone scanning.</p>

Relationship between fluorodeoxyglucose uptake and vascular endothelial growth factor in early-stage nasophygeal carcinoma / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the overexpression of vascular endothelial growth factor (VEGF) and fluorine-18 fluorodeoxyglucose (FDG) uptake in early-stage nasopharyngeal carcinoma (NPC) and evaluate their relationship.</p><p><b>METHODS</b>FDG positron emission tomography (PET) was performed in forty patients with stage I and stage II NPC. The maximum and mean standard uptake values (SUVmax and SUVmean, respectively) were measured in each patient, and the expression of VEGF was measured on paraffin sections using immunohistochemistry.</p><p><b>RESULTS</b>The FDG uptake in the patients were 9.45-/+1.87 (SUVmax) and 6.04-/+1.09 (SUVmean), 8.95-/+1.91 (SUVmax) and 6.04-/+1.09 (SUVmean) in stage I patients, and 11.55-/+1.70 (SUVmax) and 7.98-/+1.1 (SUVmean) in stage II patients. The FDG uptake of stage II patients was higher than that of stage I patients. The FDG uptake of non-keratinizing differentiated carcinoma was 9.74-/+1.82 (SUVmax) and 6.82-/+1.23 (SUVmean) and 10.44-/+2.16 (SUVmax) and 6.68-/+1.35 (SUVmean) in non-keratinizing undifferentiated carcinoma, showing no significant differences between them (SUVmax: t=1.230, P>0.05; SUVmean: t=0.346, P>0.05). The VEGF-positive cells were 60.80% in the tumor. A correlation between VEGF expression and FDG uptake in he tumor was noted (r=0.460, P=0.03).</p><p><b>CONCLUSION</b>VEGF overexpression is correlated to FDG uptake in patients with early-stage NPC. The SUV value reflects the glucose metabolism of NPC, and also shows the degree of oxygen insufficiency in the tumor tissue.</p>

Mechanism of cardiotoxicity associated with Herceptin using (131)I-Herceptin radioimmunoimaging / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the mechanism of cardiotoxicity associated with Herceptin.</p><p><b>METHODS</b>Herceptin was labeled with iodine-131 using the Iodogen method. Radioimmunoimaging was performed in 5 rabbits at 3 h to 5 days following (131)I-Herceptin injection to investigate the biodistribution of Herceptin. (131)I-Herceptin uptake in each organ or tissue relative to that in the muscular tissue (O/M ratio) was calculated and compared. On the fifth day following the injection, the organs including the heart, lung, liver and muscles were taken for measurement of the weight and radiocounts. HER2 expression was measured by immunohistochemistry in these organs and tissues.</p><p><b>RESULTS</b>The O/M ratio of the heart was significantly higher than that of the lung (P=0.032) and liver (P=0.019) at 3 h after Herceptin injection, but reduced significantly at 24 h (P=0.001). The uptake of (131)I-Herceptin in the myocardium was slightly higher that that in the muscle and intestine, but lower than that in the lung and spleen. HER2 expression showed no significant difference between the myocardium and the other tissues such as the liver, lung, and kidney (H=3.236, P=0.172).</p><p><b>CONCLUSION</b>Myocardium expresses low levels of HER2 and accumulates Herceptin no more than the other tissues.</p>

Killing effect of sequential Herceptin and adriamycin treatment on breast cancer cell line in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the killing effect of Herceptin and adriamycin sequentially applied on breast cancer cell line in vitro.</p><p><b>METHODS</b>BT-474 human breast cancer cells in exponential growth phase were treated with Herceptin alone, adriamycin alone and their sequential administration (Herceptin before adriamycin and vice versa), respectively. Under optical microscope, the morphological changes of the cells were observed before and after drug administration. The expression rate and mean fluorescence intensity (MFI) of HER-2/neu and cell death rate were detected by flow cytometry.</p><p><b>RESULTS</b>Microscopically, the cells treated with different protocols all exhibited such changes as darkening and increase of cellular debris with irregular cell morphology. Flow cytometry revealed no significant difference in the expression rate of HER-2/neu in each group before and after treatment, but the MFI of HER-2/neu and death rate of the treated cells were significant different from those of the control group (P<0.05). The cell death rate of Herceptin-pretreated cells was significantly higher than that of adriamycin-pretreated ones (P<0.05).</p><p><b>CONCLUSION</b>Herceptin pretreatment enhances the killing effect of adriamycin on breast cancer cell line BT-474, which provides experimental evidence for designing clinical sequential biochemotherapy of breast cancer.</p>

Preparation, quality control and biodistribution of 131I-herceptin in New Zealand rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the immunoactivity,biodistribution and metabolic pattern of (131)I-Herceptin in rabbits.</p><p><b>METHODS</b>Herceptin was radiolabelled with (131)I and its radiochemicalpurity (RCP) measured by size-exclusion high-pressure liquid chromatography (HPLC). The binding rate to BT-474 cells was measured to evaluate the immunoactivity of (131)I-Herceptin. (131)I-herceptin (2.0 mCi/kg) was injected intravenously into New Zealand rabbits. Scintigraphy on emission computed tomography was performed at 3 h, 1, 3 and 5 days after injection, and the radiocounts of the heart, liver and kidney etc. were compared with that of the muscle to calculate the organ-to-muscle activity ratio (O/M). On the fifth day,the rabbits were killed and the blood, myocardium, lung and other organs were obtained for measuring the radiocounts on gamma-counter to calculate the uptake percentage per gram tissue (ID%/g).</p><p><b>RESULTS</b>The labeling rate of (131)I-herceptin was 93% with RCP of 95% and binding rate to BT-474 cells of 36.9%. After injection of (131)I-herceptin, the heart, lung and liver displayed dense radioactive regions but not the muscles and intestines. Three hours after injection, the O/M ratio of the heart was significantly higher than that of the lung, kidney and intestine (P<0.05), but decreased significantly one day after injection (t=10.817, P<0.001) with further decrement on days 3 and 5 (P<0.05). The O/M ratio of liver on day 1, 3, and 5 reduced significantly in comparison with that at 3 h (P<0.05). The uptake percentage was higher in the blood (11.3 ID/g%) than in the liver (2.8 ID/g%) and the myocardium (1.8 ID/g%).</p><p><b>CONCLUSIONS</b>(131)I-herceptin possesses high immunoactivity which distributes mainly in the blood, liver and kidney, but with low uptake in the myocardium.</p>