Comparison of different SUV-based methods for monitoring cytotoxic therapy with FDG PET

Purpose Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is a promising tool for monitoring cytotoxic therapy in tumours. Due to the limited data available, a standard imaging protocol for the prediction of tumour response has not yet been approved. The aim of this study was to compare commonly applied imaging protocols and calculations of the standardised uptake value (SUV) for the early prediction of histopathological response to chemotherapy.Methods Serial FDG PET scans of 43 patients with gastric carcinomas were retrospectively analysed. All patients received two consecutive scans (one bed position at 40 min p.i. and four bed positions at 90 min p.i.) at baseline and during the first cycle of cisplatinum-based chemotherapy. Reconstruction of the images was performed by filtered back-projection (FBP) and using an iterative algorithm (OSEM). SUVs were calculated with and without correction for the blood glucose level using normalisation by body weight, body surface area and lean body mass. Relative percentage changes between SUVs at baseline and follow-up were calculated and analysed for their potential to predict histopathological response to chemotherapy (ROC analysis). Response was defined as less than 10% viable tumour cells in the tumour specimen obtained by surgery 3–4 weeks after the completion of chemotherapy.Results Eight of 43 patients were histopathological responders to chemotherapy. The percentage changes in SUV_{body weight} for responders and non-responders were –52.2 (±13.2) and –25.2 (±15.2), –54.7 (±18.2) and –24.5 (±16.1), –53.9 (±24.2) and –22.7 (±21.3), and –56.7 (±21.6) and –26.1 (±18.9) for serial scans at 40-min FBP, 40-min OSEM, 90-min FBP and 90-min OSEM, respectively (responders versus non-responders: p<0.01 in each case). According to ROC analysis, neither the scan protocol nor correction for blood glucose significantly influenced the accuracy (approx. 80%) or the cut-off value (approx. –40% change in tumour SUV) for the prediction of response. Normalisation of SUVs by body surface area or lean body mass instead of body weight yielded essentially identical results.Conclusion In gastric carcinomas the prediction of response to chemotherapy on the basis of relative tumour SUV changes is not essentially influenced by any of the methodological variations investigated (time delay after FDG administration, acquisition protocol, reconstruction algorithm, normalisation of SUV). This demonstrates the robustness of FDG PET for therapeutic monitoring and facilitates the comparability of studies obtained at different institutions and with different protocols. However, whichever method is used for therapy monitoring with FDG PET, a highly standardised protocol must be observed to take the dynamics of tumour FDG uptake into account.     

Prognostic significance of total lesion glycolysis in patients with advanced non-small cell lung cancer receiving chemotherapy

Background

[¹⁸F]fluorodeoxyglucose positron emission tomography (FDG-PET) imaging has been employed as a non-invasive diagnostic tool for malignant tumors. Total lesion glycolysis (TLG) on FDG-PET is calculated by multiplying the mean standardized uptake value (SUVmean) by the tumor volume. Unlike the maximum standardized uptake value (SUVmax), which represents the point of greatest metabolic activity within tumors, TLG has been suggested to reflect global metabolic activity in whole tumors.

Methods

We retrospectively examined whether or not FDG-PET measurements, including SUVmean, SUVmax, and TLG, could predict progression-free survival (PFS) or overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving chemotherapy.

Results

This study involved 81 consecutive patients with NSCLC who received chemotherapy. All of the patients underwent FDG-PET examination before treatment. SUVmean, SUVmax, and TLG on FDG-PET were significantly associated with gender, smoking status, and tumor histology. With adjustment for several other variables, Cox regression analysis showed that TLG was significantly prognostic for both PFS [hazard ratio = 2.34; 95% confidence interval, 1.18–4.64; P = 0.015] and OS (hazard ratio = 2.80; 95% confidence interval, 1.12–6.96; P = 0.003), whereas SUVmean and SUVmax had no significant association with PFS (P = 0.693 and P = 0.322, respectively) or OS (P = 0.587 and P = 0.214, respectively).

Conclusions

Our findings suggest that TLG may be more useful than SUVmean and SUVmax for predicting PFS and OS in NSCLC patients receiving chemotherapy. The TLG measurement on FDG-PET imaging could be routinely recommended to advanced NSCLC patients.     

RNA干扰沉默急性白血病细胞SUV39H1基因表达的实验研究

目的 应用小干扰RNA(siRNA)干扰人急性髓系白血病细胞株KG-1细胞SUV39H1(suppressor of variegation 3-9 homolog 1)基因的表达,研究SUV39H1基因沉默对KG-1细胞增殖、抑癌基因p15表达及组蛋白甲基化、乙酰化修饰的影响,探寻白血病基因治疗的新靶点.方法 用LipofectamineTM2000将体外合成针对SUV39H1基因的siRNA片段转染到KG-1细胞后,采用RT-PCR方法检测siRNA对SUV39H1 mRNA表达的抑制效果,用四唑氮化合物(MTS)法绘制细胞增殖抑制曲线,Western blot法检测目的 基因SUV39H1和抑癌基因p15的表达及对组蛋白甲基化、乙酰化修饰的影响.结果 SUV39H1 siRNA转染KG-1细胞可沉默该基因;沉默SUV39H1基因表达可抑制细胞增殖,30、60、120、240 nmol/L SUV39H1 siRNA转染48 h后,KG-1细胞的增殖抑制率分别为(23.57±1.98)%、(48.69±1.84)%、(62.69±1.61)%、(81.06±3.22)%,差异有统计学意义(P<0.05);沉默SUV39H1基因可上调p15基因的表达,下调组蛋白H3K9三甲基化,上调组蛋白H3K9、H3的乙酰化.30、60、120 nmol/L SUV39H1 siRNA处理KG-1细胞48 h后,组蛋白H3K9三甲基化水平较对照组分别减少25%、33%、49%;组蛋白H3K9乙酰化水平增强,分别为对照组的1.83、2.16、3.07倍;组蛋白H3乙酰化水平逐渐升高为对照组的1.35、1.87、2.37倍;p15表达水平呈递增趋势,分别为对照组的1.52、2.89、3.08倍;而组蛋白H4、H3K14、H3K27的乙酰化水平未见显著变化.结论 沉默SUV39H1基因表达可能通过改变抑癌基因启动子区域的组蛋白修饰,即上调组蛋白H3K9乙酰化及下调H3K9甲基化,使p15基因重新表达,从而抑制细胞增殖.     

Differentiation of adrenal incidentalomas by qualitative and quantitative analytical data obtained by 18F-FDG positron emission tomography/computed tomography in cancer patients

Aim of the work

To evaluate the diagnostic reliability of qualitative and quantitative data of 18F-FDG PET/CT scanning in the identification and differentiation of adrenal incidentalomas discovered in cancer patients.

Stable isotope-resolved metabolomics and applications for drug development

Advances in analytical methodologies, principally nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS), during the last decade have made large-scale analysis of the human metabolome a reality. This is leading to the reawakening of the importance of metabolism in human diseases, particularly cancer. The metabolome is the functional readout of the genome, functional genome, and proteome; it is also an integral partner in molecular regulations for homeostasis. The interrogation of the metabolome, or metabolomics, is now being applied to numerous diseases, largely by metabolite profiling for biomarker discovery, but also in pharmacology and therapeutics. Recent advances in stable isotope tracer-based metabolomic approaches enable unambiguous tracking of individual atoms through compartmentalized metabolic networks directly in human subjects, which promises to decipher the complexity of the human metabolome at an unprecedented pace. This knowledge will revolutionize our understanding of complex human diseases, clinical diagnostics, as well as individualized therapeutics and drug response.In this review, we focus on the use of stable isotope tracers with metabolomics technologies for understanding metabolic network dynamics in both model systems and in clinical applications. Atom-resolved isotope tracing via the two major analytical platforms, NMR and MS, has the power to determine novel metabolic reprogramming in diseases, discover new drug targets, and facilitates ADME studies. We also illustrate new metabolic tracer-based imaging technologies, which enable direct visualization of metabolic processes in vivo. We further outline current practices and future requirements for biochemoinformatics development, which is an integral part of translating stable isotope-resolved metabolomics into clinical reality.     

99Tcm-MDP骨显像SUV值在鼻咽癌颅底侵犯诊断价值初步研究

目的通过传统99Tc^m-MDP(锝-99亚甲基二膦酸盐)全身骨单光子发射计算机断层成像术/电子计算机断层扫描(single-photon emission computed tomography/computed tomography,SPECT/CT)显像,计算鼻咽癌患者颅底骨质基于放射活度的标准摄取值(standardized uptake value,SUV),观察99Tc^m-MDP全身骨SPECT/CT显像中的颅底区域SUV对鼻咽癌颅底骨质侵犯的增益价值及阳性诊断的最佳SUV界值范围。方法选取2016年6月至2017月1月本院确诊鼻咽癌并行全身骨显像患者51例,男40例,女11例,年龄27~77岁,平均年龄50.4±10.7岁,其中28例鼻咽部磁共振成像(magnetic resonance imaging,MRI)证实伴颅底骨质侵犯,23例鼻咽部MRI证实未见颅底骨质侵犯。通过定量分析软件分析融合图像,勾勒感兴趣区(region of interest,ROI),测得颅底骨质侵犯组及颅底骨质非侵犯组的最大标准化摄取值(SUVmax)及平均标准化摄取值(SUVmean),并采用t检验和受试者工作特征曲线(receiver operating characteristic curve,ROC)计算两组的界值。结果颅底骨质侵犯组28例SUVmax平均值为3.17(标准差为1.38);颅底骨质非侵犯组23例SUVmax平均值为1.34(标准差为0.39)。两组比较,t=6.129,P<0.001,差异有统计学意义。颅底骨质侵犯组28例SUVmean平均值为0.45(标准差为0.16);颅底骨质非侵犯组23例SUVmean平均值为0.9(标准差为0.37)。两组比较,t=5.80,P<0.001,差异有统计学意义。51例鼻咽癌患者的SUVmax按颅底骨质侵犯组和颅底骨质非侵犯组进行ROC曲线分析,曲线下面积为0.961,阈值为1.85时,灵敏度为89%,特异性为92%;51例鼻咽癌患者的SUVmean按颅底骨质侵犯组和颅底骨质非侵犯组进行ROC曲线分析,曲线下面积为0.904,阈值为0.55时,灵敏度为82%,特异性为79%。结论全身骨SPECT/CT显像测得基于放射活度的SUV值与鼻咽癌颅底骨质侵犯与否具有良好的相关性,因此SPECT/CT SUV值为鼻咽癌全身骨SPECT/CT显像提供了一种新的具有较高的准确性辅助诊断信息,初步得出在SUVmax为1.85时其对鼻咽癌颅底骨质侵犯诊断价值较高,故SUVmax为1.85可作为最佳诊断阈值。     

Disposition of intact liposomes of different compositions and of liposomal degradation products

Small unilamellar liposomes containing bovine serum albumin were prepared by a new double-emulsion technique and administered to mice and rats in intravenous injections. The elimination of intact liposomes, the association of phospholipid marker with lipoproteins, and the appearance of released internal marker and its degradation products were followed by column chromatography of plasma samples. In vitro labelled lipoproteins were administered to the animals in intravenous injections together with free bovine serum albumin and the elimination of the two substances was studied by closely related techniques. The clearance of intact PC:PS (4:1) liposomes from plasma was biphasic and much faster than that of labelled lipoproteins and bovine serum albumin either originating from liposomes or injected as such. The second elimination phase for these liposomes was barely detectable by our analytical methods. In contrast, DSPC:CHOL (2:1) liposomes showed a very significant second-phase elimination, with a half-life of 12 hr for the intact liposomes. In tissue distribution studies in mice, the major accumulation of liposomal markers was found in the liver and spleen, and less in the kidneys and intestinal wall. Uptake into liver and spleen appeared to be due to the uptake of intact liposomes, whereas the uptake into kidneys and gut wall was caused by the uptake of liposomal degradation products. The uptake of PC:PS (4:1) liposomes into the liver was higher than that of DSPC:CHOL (2:1) liposomes; the opposite was the case with their uptake into the spleen. In rats, too, liposomes of different compositions showed significant variations in stability and in plasma half-lives of intact liposomes. Generally, there was a considerable increase in the liposomal stability in the presence of cholesterol and when use was made of a phospholipid with a high transition temperature.