Metabolic fate of 18F-FDG in mice bearing either SCCVII squamous cell carcinoma or C3H mammary carcinoma.

Tumors often have an increased uptake of glucose and can be detected by PET imaging using 18F-FDG. 18F-FDG is converted to 18F-FDG-6-phosphate (18F-FDG-6-P), and the usual assumption is that 18F-FDG-6-P is not a substrate for subsequent enzymatic reactions and that tumor hot spots reflect trapping of 18F-FDG-6-P. We recently found, however, that in the pig liver, 18F-FDG is metabolized not only to 18F-FDG-6-P but also to the subsequent oxygenation product 2-18F-fluoro-2-deoxy-6-phospho-D-glucononate (18F-FD-PG1). We therefore wished to characterize the metabolism of 18F-FDG in experimental tumors in mice. METHODS: 18F-FDG was given intravenously to mice with either SCCVII squamous cell carcinoma or C3H mammary carcinoma grown on the back. 18F-Labeled metabolites were determined by radio-high-performance liquid chromatography in tumor tissue biopsies, in a time course of 180 min (12 mice of each tumor type), and in liver tissue biopsies 80 min after tracer injection (2 mice of each type). RESULTS: After the tracer injection, not only 18F-FDG and 18F-FDG-6-P but also 18F-FD-PG1 and 2-18F-fluoro-2-deoxy-1,6-biphosphate were detected in both tumors, relatively more in SCCVII carcinoma than in C3H carcinoma. Both tumors accumulated radioactivity throughout the 180-min measurement period, 4-fold more in SCCVII carcinoma than in C3H carcinoma. At 80 min, the radioactivity was approximately 6 and 1.2 times higher in the respective tumors than in liver tissue. CONCLUSION: Our results agree with the general finding that most malignant tumor tissues accumulate significantly more 18F-radioactivity than do normal tissues, but our results do not support the concept that this increase is caused solely by accumulation of 18F-FDG-6-P. Furthermore, the rate of 18F-FDG metabolism was higher in SCCVII carcinoma than in C3H carcinoma.     

Response of mammary tumors of C3H/He mice to hyperthermia and bleomycin in vivo

The cytotoxicity of bleomycin in vitro has previously been shown to be enhanced by hyperthermia. This study demonstrates in vivo a synergistic interaction between local hyperthermia (43 degrees C, 45 min) and bleomycin (15 mg/kg) against implanted mammary tumors of C3H/He mice. Hyperthermia was given by water bath heating. When combined treatments of heat and bleomycin were administered within 30 min of each other, a synergistic effect was observed. In contrast, when the interval between heat and bleomycin injection was longer than 30 min, only an additive effect was obtained. Timing is therefore considered to be a critical factor for the optimal combination of hyperthermia and bleomycin.     

Response of human organs to single (or fractionated equivalent) doses of irradiation

Characteristics of the kinetics of radiation response of human tissues and organs are exemplified by effects in the testis and the ovary. Also, published dose-incidence curves for specified levels of injury in bone marrow, liver, bladder and lung are characterised in terms of single doses as well as single-dose equivalents calculated from fractionated doses using the alpha/beta equation. It is shown that these curves, analysed using a Poisson model, have slopes characterised by D0-equivalents ranging between 1.25 and 2.5 Gy. These values are higher or within the range of values reported in general for single-dose survival curves of human cells in primary culture (range of D0 values 0.7-1.8 Gy). This indicates that single-cell responses together with other complicating biological and statistical sources of heterogeneity under discussion, could form a basis for explaining the steepness of dose-incidence curves for organ injury after fractionated doses. With local organ irradiation, increase in the single-dose equivalent by 3-10 per cent would increase the complication rate from 5 per cent to 10 per cent. Higher dosage increases (by up to two times) apply to fractionated doses.     

多肿瘤抑制基因对卵巢癌细胞周期的影响

目的：在以往研究的基础上进一步探讨多肿瘤抑制基因（MTSI）对卵巢癌细胞周期的影响。方法：将卵巢癌细胞（HO8910）和转染空载体的卵巢癌细胞（8910－pcDNA2)作为对照组,与转染MTS1的卵巢癌细胞（8910－p16)同时进行消化收集后经流式细胞仪检测,对比各组间细胞周期的改变。结果：HO－8910细胞经MTS1转染后,其受阻于G1期的细胞增多,同时S期细胞相应减少,而单纯转染空载体并不对细胞周期产生任何影响。结论：MTS1基因可以改变卵巢癌细胞HO－8910的细胞周期,这可能为卵巢癌的基因治疗提供了新的实验依据。     

外照射联合瘤内注射~(131)I-chTNT对荷Lewis瘤小鼠肿瘤的治疗作用

目的 研究外照射联合瘤内注射~(131)I-肿瘤细胞核人鼠嵌合单克隆抗体(chTNT)对荷瘤小鼠肿瘤生长和体内放射性分布的影响.方法 建立C57BL近交系荷Lewis瘤小鼠模型64只,当肿瘤直径达6.0 mm时,用随机数字法分组进行荷瘤小鼠体内分布实验(18只)及~(131)I-chTNT显像(6只),均分为单药组和外照射联合组(小鼠分配9只×2和3只×2),观察给药后1,3和5 d肿瘤组织及血液、对侧大腿肌肉、胃、肝、肾、心、肺的放射性,用每克组织百分注射剂量率(%ID/g)表示;肿瘤生长效应实验设4个组(每组10只):对照组、单药组、外照射组和联合组,观察指标为肿瘤生长延迟时间.采用SPSS 11.5软件,组间比较行t检验.结果 荷瘤小鼠体内分布实验中联合组肿瘤组织放射性在1[(11.95±1.33)%ID/g]和3 d[(9.38±1.25)%ID/g]均高于单药组[(7.86±0.94)和(6.57±0.71)%ID/g],2组间差异有统计学意义(t值分别为4.326,3.555,P均<0.05).2组中正常组织的放射性差异均无统计学意义(t值0.118～1.445,P>0.05).~(131)I-chTNT显像结果 示外照射可增加荷瘤小鼠瘤内~(131)I-chTNT的滞留量,并延长其滞留时间;生长效应实验示:单药组、外照射组的绝对延迟时间分别为(3.3±1.75)和(6.0 4±2.02)d,联合组的绝对延迟时间为(9.5±1.93)d,标准化延迟时间为6.2 d,~(131)I-chTNT对放射治疗的增效因子为1.03.结论 外照射联合瘤内注射~(131)I-chTNT可增加瘤内~(131)I-chTNT的滞留量,并延长其滞留时间,二者联合应用可提高对荷瘤小鼠肿瘤的治疗效果.     

Region-specific reduction of parvalbumin neurons and behavioral changes in adult mice following single exposure to cranial irradiation

Abstract

Purpose: Ionizing irradiation has several long-term effects including progressive cognitive impairment. Cognitive deterioration generally appears to be caused by abnormalities in the hippocampal dentate gyrus, with abnormal function of parvalbumin-expressing interneurons (PV neurons) in the cerebral cortex. PV neurons are vulnerable to oxidative stress, which can be caused by ionizing irradiation. We speculated that selective impairment of specific brain regions due to ionizing irradiation may alter the degree of cognitive impairment.

Methods: We irradiated mature mouse brains with 20?Gy-ionizing irradiation. Subsequently, we analyzed behavioral abnormalities and changes in the number of PV neurons.

Results: PV neuron density was significantly lower in some cortical regions of irradiated mice than in control mice. Within 1 week of irradiation, both body weight and temperature of irradiated mice decreased. In the forced swim test, irradiated mice spent significantly less time immobile than did control mice. However, irradiated mice did not display any abnormalities in the elevated plus maze test, Y-maze test, tail suspension test, and social interaction test between 3 to 6 days after irradiation.

Conclusions: These results suggest that high-dose irradiation is less likely to cause brain dysfunction in the subacute phase. Moreover, the vulnerability of PV neurons appears to be brain-region specific.     

小细胞肺癌三种全脑预防性照射计划的剂量学比较

目的 比较小细胞肺癌(SCLC)全脑预防性照射(PCI)3D-CRT、IMRT、RapidArc 3种计划方式的剂量学差异,为制定最佳PCI放疗方案提供指导。方法 选取10例SCLC患者颅脑CT,分别设计3D-CRT、IMRT及RapidArc 3种放疗计划。根据剂量体积直方图,评价靶区的D_2%、D_98%、V₉₅、V₁₀₀、均匀性指数(HI)、适形性指数(CI)以及危及器官(OAR)受量,比较机器跳数(MU)的差异。 结果 IMRT及RapidArc的靶区剂量学参数(CI、HI、D_2%、D_98%、V₉₅、V₁₀₀)均优于3D-CRT,差异有统计学意义(P<0.05)。IMRT、RapidArc较3D-CRT显著降低左右视神经D_max、左右腮腺D_mean及脑干D_max的受量,差异有统计学意义(P<0.05);相反,3D-CRT能显著减少左右晶状体的D_max和左右眼球的D_max、D_mean受量,差异有统计学意义(P<0.05)。IMRT及RapidArc在靶区和危及器官受量方面无差异。3D-CRT、IMRT和RapidArc计划的平均MU分别为287.8、1388.8和346.6。 结论 IMRT及RapidArc较3D-CRT具有一定的剂量学优势,3D-CRT能减少晶状体及眼球的受量,治疗时间短。