Role of acetyl-L-carnitine in the brain: revealed by Bioradiography

To elucidate the role of acetyl-l-carnitine in the brain, we used a novel method, ‘Bioradiography,’ in which the dynamic process could be followed in living slices by use of positron-emitter labeled compounds and imaging plates. We studied the incorporation of 2-[¹⁸F]fluoro-2-deoxy-d-glucose ([¹⁸F]FDG) into rat brain slices incubated in oxygenated Krebs-Ringer solution. Under the glucose-free condition, [¹⁸F]FDG uptake rate decreased with time and plateaued within 350 min in the cerebral cortex and cerebellum, and the addition of 1 or 5 mM acetyl-l-carnitine did not alter the [¹⁸F]FDG uptake rate. When a glutaminase inhibitor, 0.5 mM 6-diazo-5-oxo-l-norleucine (DON), was added under the normal glucose condition, [¹⁸F]FDG uptake rate decreased. Acetyl-l-carnitine (1 mM), which decreased [¹⁸F]FDG uptake rate, reversed this DON-induced decrease in [¹⁸F]FDG uptake rate in the cerebral cortex. These results suggest that acetyl-l-carnitine can be used for the production of releasable glutamate rather than as an energy source in the brain.     

A case of metastatic leptomeningeal carcinomatosis from early gastric carcinoma

Intramuscular myxoma is a rare benign soft tissue tumor which may be mistaken for other benign and low-grade malignant myxoid neoplasms. We present the case of a 63-year-old woman with an asymptomatic intramuscular myxoma discovered incidentally on a whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography. PET images showed a mild FDG uptake (maximum standardized uptake value, 1.78) in the left gluteus maximus. Subsequent magnetic resonance (MR) imaging revealed a well-defined ovoid mass with homogenous low signal intensity on T1-weighted sequences and markedly high signal intensity on T2-weighted sequences. Contrast-enhanced MR images showed heterogeneous enhancement throughout the mass. The diagnosis of intramuscular myxoma was confirmed on histopathology after surgical excision of the tumor. The patient had no local recurrence at one year follow-up. Our case suggests that intramuscular myxoma should be considered in the differential diagnosis of an oval-shaped intramuscular soft tissue mass with a mild FDG uptake.     

2-Deoxy-2-Fluoro-d-Glucose as a Functional Probe for NMR: The Unique Metabolism Beyond Its 6-Phosphate

Abstract: Epimeric conversion of 2-deoxy-2-fluoro- d -glucose (FDG) to its 2-epimer 2-deoxy-2-fluoro- d -mannose (FDM) proved by ¹⁹F NMR has been shown to reflect the brain activity. To examine the feasibility of FDG as a new NMR probe for in vivo functional monitoring, we studied here the fundamental NMR properties of metabolites, spectral assignments, and reliability of NMR quantification. Metabolites confirmed in brain besides FDM-6-phosphate were as follows: FDG-1-phosphate, FDG-1,6-bisphosphate, FDM-1-phosphate, FDM-1,6-bisphosphate, and FDG and FDM derivatives of nucleotide diphosphate. NMR quantification of these metabolites was evaluated in comparison with the method of ¹⁸F-labeled FDG. In the NMR functional study using FDG, where a high dose is inevitable, the dose dependence of uptake was investigated. FDG uptake in mouse brain was shown to be in the range of interpretation using the biochemical parameters of enzymes for glucose uptake as long as a dose of <200 mg/kg was used.     

Prognostic Value of SUVmax Measured by Pretreatment Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Ewing Sarcoma

AimThe aim of this retrospective study was to determine whether glucose metabolism assessed by using Fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) provides prognostic information independent of established prognostic factors in patients with Ewing sarcoma.MethodsWe retrospectively reviewed the medical records of 34 patients (men, 19; women, 15; mean age, 14.5 ± 9.7 years) with pathologically proven Ewing sarcoma. They had undergone F-18 FDG PET/CT as part of a pretreatment workup between September 2006 and April 2012. In this analysis, patients were classified by age, sex, initial location, size, and maximum standardized uptake value (SUVmax). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier method with the log-rank test and Cox’s proportional hazards regression model.ResultsThe median survival time for all 34 subjects was 999 days and the median SUV by using PET/CT was 5.8 (range, 2–18.1). Patients with a SUVmax ≤ 5.8 survived significantly longer than those with a SUVmax > 5.8 (median survival time, 1265 vs. 656 days; p = 0.002). Survival was also found to be significantly related to age (p = 0.024), size (p = 0.03), and initial tumor location (p = 0.036). Multivariate analysis revealed that a higher SUVmax (p = 0.003; confidence interval [CI], 3.63–508.26; hazard ratio [HR], 42.98), older age (p = 0.023; CI, 1.34–54.80; HR, 8.59), and higher stage (p = 0.03; CI, 1.21–43.95; HR, 7.3) were associated with worse overall survival.ConclusionsSUVmax measured by pretreatment F-18-FDG PET/CT can predict overall survival in patients with Ewing sarcoma.     

Metformin abolishes increased tumor 18F-2-fluoro-2-deoxy-D-glucose uptake associated with a high energy diet

Insulin regulates glucose uptake by normal tissues. Although there is evidence that certain cancers are growth-stimulated by insulin, the possibility that insulin influences tumor glucose uptake as assessed by ¹⁸F-2-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography (FDG-PET) has not been studied in detail. We present a model of diet-induced hyperinsulinemia associated with increased insulin receptor activation in neoplastic tissue and with increased tumor FDG-PET image intensity. Metformin abolished the diet-induced increases in serum insulin level, tumor insulin receptor activation and tumor FDG uptake associated with the high energy diet but had no effect on these measurements in mice on a control diet. These findings provide the first functional imaging correlate of the well-known adverse effect of caloric excess on cancer outcome. They demonstrate that, for a subset of neoplasms, diet and insulin are variables that affect tumor FDG uptake and have implications for design of clinical trials of metformin as an antineoplastic agent.     

Should patients with an incidental finding of focal myocardial 18FDG uptake be screened by myocardial perfusion scintigraphy?

PurposeFocal F-18-fluoro-deoxy-glucose uptake in the myocardium can be a sign of resting myocardial ischemia. The purpose of our study was to assess the relevance of performing myocardial perfusion scintigraphy to screen for myocardial ischemia in patients with an incidental finding of focal myocardial F-18-fluoro-deoxy-glucose uptake on a routine F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography.MethodsIn our retrospective multicentric study, patients were included if they had had an incidental finding of myocardial focal F-18-fluoro-deoxy-glucose uptake on a routine F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography and had also undergone myocardial perfusion scintigraphy within 3 months before or after the F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography. Patients with a pattern of ischemia or scar on the myocardial perfusion scintigraphy in the same territory as the focal F-18-fluoro-deoxy-glucose uptake were considered positive.ResultsSeven of the 34 included patients were positive, with an abnormality on the MPS data in the same territory as the focal myocardial F-18-fluoro-deoxy-glucose uptake. 2 of the 6 patients with focal F-18-fluoro-deoxy-glucose uptake in the left anterior descending vascular supply territory and 2 of the 4 patients with focal F-18-fluoro-deoxy-glucose uptake in the standard right coronary artery territory had an abnormal myocardial perfusion scintigraphy. All 12 patients with focal F-18-fluoro-deoxy-glucose uptake restricted to the basal anterolateral and basal inferolateral segments were negative.ConclusionPatients with an incidental finding of focal F-18-fluoro-deoxy-glucose uptake on a routine F-18-fluoro-deoxy-glucose positron-emission-tomography-computed-tomography may be considered as being at risk for coronary artery disease, when this uptake is multisegmentary in the same typical coronary territory and not restricted to the basal anterolateral and basal inferolateral segments.     

Comparison of the Prognostic Value of F-18 Pet Metabolic Parameters of Primary Tumors and Regional Lymph Nodes in Patients with Locally Advanced Cervical Cancer Who Are Treated with Concurrent Chemoradiotherapy

Objective

This study investigated the metabolic parameters of primary tumors and regional lymph nodes, as measured by pre-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) to compare the prognostic value for the prediction of tumor recurrence. This study also identified the most powerful parameter in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy.

Methods

Fifty-six patients who were diagnosed with cervical cancer with pelvic and/or paraaortic lymph node metastasis were enrolled in this study. Metabolic parameters including the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors and lymph nodes were measured by pre-treatment F-18 FDG PET/CT. Univariate and multivariate analyses for disease-free survival (DFS) were performed using the clinical and metabolic parameters.

Results

The metabolic parameters of the primary tumors were not associated with DFS. However, DFS was significantly longer in patients with low values of nodal metabolic parameters than in those with high values of nodal metabolic parameters. A univariate analysis revealed that nodal metabolic parameters (SUVmax, MTV and TLG), paraaortic lymph node metastasis, and post-treatment response correlated significantly with DFS. Among these parameters, nodal SUVmax (hazard ratio [HR], 4.158; 95% confidence interval [CI], 1.1–22.7; p = 0.041) and post-treatment response (HR, 7.162; 95% CI, 1.5–11.3; p = 0.007) were found to be determinants of DFS according to a multivariate analysis. Only nodal SUVmax was an independent pre-treatment prognostic factor for DFS, and the optimal cutoff for nodal SUVmax to predict progression was 4.7.

Conclusion

Nodal SUVmax according to pre-treatment F-18 FDG PET/CT may be a prognostic biomarker for the prediction of disease recurrence in patients with locally advanced cervical cancer.     

Organ and tumor distribution of (18F)-2-fluoro-2-deoxy-D-glucose in fasting and non-fasting rats

Differences in the uptake of (18F)-2-fluoro-2-deoxy-D-glucose ((18F)FDG) in various normal organs and the Rous sarcoma of fasted and unfasted rats were studied at 5, 15, 30, 60, and 120 minutes after i.v. injection. The uptake of (18F)FDG in the tumor, spleen, and testis increased for 120 minutes, while uptake in the other organs was either level (brain, heart, white fat) or cleared off. The uptake was higher in the tumor than in the normal organs. The fraction of viable tumor tissue as measured morphometrically correlated intraindividually with the uptake of (18F)FDG--an increase of 1% of vital tumor corresponded to a 1.01-fold increase in tumor uptake of (18F)FDG. The nutritional state was of importance for the uptake of (18F)FDG into the heart, testis and brown fat. (18F)FDG is taken quantitatively up by the viable parts of the Rous tumor; this may make it possible to follow the response of treatment in individual tumors also in man with (18F)FDG and positron emission tomography (PET).     

Non‐invasive imaging of allogeneic transplanted skin graft by 131I‐anti‐TLR5 mAb

Although ¹⁸F‐fluorodeoxyglucose (¹⁸F‐FDG) uptake can be used for the non‐invasive detection and monitoring of allograft rejection by activated leucocytes, this non‐specific accumulation is easily impaired by immunosuppressants. Our aim was to evaluate a ¹³¹I‐radiolabelled anti‐Toll‐like receptor 5 (TLR5) mAb for non‐invasive in vivo graft visualization and quantification in allogeneic transplantation mice model, compared with the non‐specific radiotracer ¹⁸F‐FDG under using of immunosuppressant. Labelling, binding, and stability studies were performed. BALB/c mice transplanted with C57BL/6 skin grafts, with or without rapamycin treatment (named as allo‐treated group or allo‐rejection group), were injected with ¹³¹I‐anti‐TLR5 mAb, ¹⁸F‐FDG, or mouse isotype ¹³¹I‐IgG, respectively. Whole‐body phosphor‐autoradiography and ex vivo biodistribution studies were obtained. Whole‐body phosphor‐autoradiography showed ¹³¹I‐anti‐TLR5 mAb uptake into organs that were well perfused with blood at 1 hr and showed clear graft images from 12 hrs onwards. The ¹³¹I‐anti‐TLR5 mAb had significantly higher graft uptake and target‐to‐non‐target ratio in the allo‐treated group, as determined by semi‐quantification of phosphor‐autoradiography images; these results were consistent with ex vivo biodistribution studies. However, high ¹⁸F‐FDG uptake was not observed in the allo‐treated group. The highest allograft‐skin‐to‐native‐skin ratio (A:N) of ¹³¹I‐anti‐TLR5 mAb uptake was significantly higher than the ratio for ¹⁸F‐FDG (7.68 versus 1.16, respectively). ¹³¹I‐anti‐TLR5 mAb uptake in the grafts significantly correlated with TLR5 expression in the allograft area. The accumulation of ¹³¹I‐IgG was comparable in both groups. We conclude that radiolabelled anti‐TLR5 mAb is capable of detecting allograft with high target specificity after treatment with the immunosuppressive drug rapamycin.     

Monitoring the correction of glycogen storage disease type 1a in a mouse model using [(18)F]FDG and a dedicated animal scanner

Monitoring gene therapy of glycogen storage disease type 1a in a mouse model was achieved using [(18)F]FDG and a dedicated animal scanner. The G6Pase knockout (KO) mice were compared to the same mice after infusion with a recombinant adenovirus containing the murine G6Pase gene (Ad-mG6Pase). Serial images of the same mouse before and after therapy were obtained and compared with wild-type (WT) mice of the same strain to determine the uptake and retention of [(18)F]FDG in the liver. Image data were acquired from heart, blood pool and liver for twenty minutes after injection of [(18)F]FDG. The retention of [(18)F]FDG was lower for the WT mice compared to the KO mice. The mice treated with adenovirus-mediated gene therapy had retention similar to that found in age-matched WT mice. These studies show that FDG can be used to monitor the G6Pase concentration in liver of WT mice as compared to G6Pase KO mice. In these mice, gene therapy returned the liver function to that found in age matched WT controls as measured by the FDG kinetics in the liver compared to that found in age matched wild type controls.     

6-Fluoro-6-deoxy-D-glucose as a tracer of glucose transport

Glucose transport rates are estimated noninvasively in physiological and pathological states by kinetic imaging using PET. The glucose analog most often used is (18)F-labeled 2FDG. Compared with glucose, 2FDG is poorly transported by intestine and kidney. We examined the possible use of 6FDG as a tracer of glucose transport. Lacking a hydroxyl at its 6th position, 6FDG cannot be phosphorylated as 2FDG is. Prior studies have shown that 6FDG competes with glucose for transport in yeast and is actively transported by intestine. Its uptake by muscle has been reported to be unresponsive to insulin, but that study is suspect. We found that insulin stimulated 6FDG uptake 1.6-fold in 3T3-L1 adipocytes and azide stimulated the uptake 3.7-fold in Clone 9 cells. Stimulations of the uptake of 3OMG, commonly used in transport assays, were similar, and the uptakes were inhibited by cyclochalasin B. Glucose transport is by GLUT1 and GLUT4 transporters in 3T3-L1 adipocyte and by the GLUT1 transporter in Clone 9 cells. Cytochalasin B inhibits those transporters. Rats were also imaged in vivo by PET using 6(18)FDG. There was no excretion of (18)F into the urinary bladder unless phlorizin, an inhibitor of active renal transport, was also injected. (18)F activity in brain, liver, and heart over the time of scanning reached a constant level, in keeping with the 6FDG being distributed in body water. In contrast, (18)F from 2(18)FDG was excreted in relatively large amounts into the bladder, and (18)F activity rose with time in heart and brain in accord with accumulation of 2(18)FDG-6-P in those organs. We conclude that 6FDG is actively transported by kidney as well as intestine and is insulin responsive. In trace quantity, it appears to be distributed in body water unchanged. These results provide support for its use as a valid tracer of glucose transport.     

Lumped constant for [(18)F]fluorodeoxyglucose in skeletal muscles of obese and nonobese humans

Quantitative 2-[(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) positron emission tomography (PET) has been widely used to calculate glucose utilization in skeletal muscle. FDG-PET results depend partly on the lumped constant (LC), which accounts for the differences in the transport and phosphorylation between [(18)F]FDG and glucose. In this study, we estimated the LC for [(18)F]FDG directly in normal and in insulin-resistant obese subjects by combining FDG PET with the microdialysis technique. Eight obese [age 29.4 +/- 1.0 yr, body mass index (BMI) 33.6 +/- 1.0 kg/m(2)] and eight nonobese (age 25.0 +/- 1.0 yr, BMI 23.1 +/- 1.0 kg/m(2)) males were studied during euglycemic hyperinsulinemia (1 mU. kg(-1).min(-1) for 150 min). Muscle blood flow was measured using (15)O-labeled water and PET. Muscle [(18)F]FDG uptake (rGU(FDG)) was calculated with Patlak graphic analysis. Interstitial glucose concentration of the quadriceps femoris muscle was measured simultaneously with [(18)F]FDG scanning using microdialysis. Muscle glucose uptake (by microdialysis, rGU(MD)) was calculated by multiplying glucose extraction by regional muscle blood flow. A significant correlation was found between rGU(MD) and rGU(FDG) (r = 0.78, P < 0.01). The LC was determined as the ratio of the rGU(FDG) to the rGU(MD). The LC averaged 1.16 +/- 0.16 and was similar in the obese and nonobese subjects (1.15 +/- 0.11 vs. 1.16 +/- 0.07, respectively, not significant). In conclusion, the microdialysis technique can be reliably combined with FDG PET to measure glucose uptake in skeletal muscle. Direct measurements with these two independent techniques suggest an LC value of 1.2 for [(18)F]FDG in human skeletal muscle during insulin stimulation, and the LC appears not to be sensitive to insulin resistance.     

Gated F-18 FDG PET for Assessment of Left Ventricular Volumes and Ejection Fraction Using QGS and 4D-MSPECT in Patients with Heart Failure: A Comparison with Cardiac MRI

Purpose

Ventricular function is a powerful predictor of survival in patients with heart failure (HF). However, studies characterizing gated F-18 FDG PET for the assessment of the cardiac function are rare. The aim of this study was to prospectively compare gated F-18 FDG PET and cardiac MRI for the assessment of ventricular volume and ejection fraction (EF) in patients with HF.

Methods

Eighty-nine patients with diagnosed HF who underwent both gated F-18 FDG PET/CT and cardiac MRI within 3 days were included in the analysis. Left ventricular (LV) end-diastolic volume (EDV), end-systolic volume (ESV), and EF were obtained from gated F-18 FDG PET/CT using the Quantitative Gated SPECT (QGS) and 4D-MSPECT software.

Results

LV EDV and LV ESV measured by QGS were significantly lower than those measured by cardiac MRI (both P<0.0001). In contrast, the corresponding values for LV EDV for 4D-MSPECT were comparable, and LV ESV was underestimated with borderline significance compared with cardiac MRI (P = 0.047). LV EF measured by QGS and cardiac MRI showed no significant differences, whereas the corresponding values for 4D-MSPECT were lower than for cardiac MRI (P<0.0001). The correlations of LV EDV, LV ESV, and LV EF between gated F-18 FDG PET/CT and cardiac MRI were excellent for both QGS (r = 0.92, 0.92, and 0.76, respectively) and 4D-MSPECT (r = 0.93, 0.94, and 0.75, respectively). However, Bland-Altman analysis revealed a significant systemic error, where LV EDV (−27.9±37.0 mL) and ESV (−18.6±33.8 mL) were underestimated by QGS.

Conclusion

Despite the observation that gated F-18 FDG PET/CT were well correlated with cardiac MRI for assessing LV function, variation was observed between the two imaging modalities, and so these imaging techniques should not be used interchangeably.     

实验动物准备对裸鼠移植瘤模型microPET 显像的影响

目的 探讨实验动物准备条件对18 F-FDG microPET 裸鼠移植瘤模型显像的影响,以选择最佳的实验动物准备条件.方法 36 只人表皮样癌细胞A431 裸鼠皮下移植瘤模型.随机分为6 组（6 只/组）;A 组：无禁食、室温（20 ～22）℃、无麻醉（注射18 F-FDG 后60 min 清醒状态）、尾静脉注射18 F-FDG;B 组：禁食（6 ～8）h、加温（30 ～32）℃、麻醉（吸入2%异氟烷麻醉）、尾静脉注射18 F-FDG;C 组：无禁食、加温、麻醉、尾静脉注射18 F-FDG;D组：禁食、室温、麻醉、尾静脉注射18 F-FDG;E 组：禁食、加温、无麻醉、尾静脉注射18 F-FDG;F 组：禁食、加温、麻醉、腹腔注射18 F-FDG.注射18 F-FDG 约1 h 后,行microPET 显像,测量皮下移植瘤、颈部肌肉、棕色脂肪、脑、肝脏、肾脏、心脏、哈氏腺最大每克组织摄取率（%ID/gmax ）.扫描前裸鼠均测血糖.结果 （1）B 组、C 组、F 组裸鼠的血糖水平与肿瘤摄取之间均呈直线负相关.（2）棕色脂肪：A 组摄取最高（8.03 ±1.29）,B 组摄取降低71.98%（P ＝0.000）.颈部肌肉：A 组摄取最高（16.07 ±5.20）,B 组摄取降低最多达81.84%（P ＝0.000）.各组脑、心脏、肝脏、肾脏、哈氏腺摄取差异无统计学意义.（3）A 组皮下移植瘤/组织或器官的摄取率最低.B 组移植瘤/颈部肌肉,移植瘤/肝脏,移植瘤/棕色脂肪的摄取率较A 组分别升高6.50 倍、1.29 倍、4.76 倍（P 均＜0.05）,肿瘤与组织或器官的图像对比度明显改善.（4）第1 次microPET 显像,尾静脉注射与腹腔注射皮下移植瘤摄取值差别无统计学意义（P ＝0.364）.第2 次microPET 显像,腹腔注射腹腔可见不同程度显像剂浓聚,其他正常组织、器官及皮下移植瘤的摄取均减低.腹腔注射方式,两次皮下移植瘤的摄取值差异有统计学意义（P ＝0.025）.结论实验动物准备明显影响18 F-FDG 在裸鼠正常组织的分布及皮下移植瘤的摄取.禁食、加温、麻醉及尾静脉注射方式,可以改善肿瘤对18 F-FDG 的摄取,保证图像有较好的稳定性及可重复性.     

La fixation vasculaire du 18FDG est reliée au risque d’événements récents ou futurs chez les patients à haut risque cardiovasculaire

With this study, we sought to identify plaque inflammation as assessed by ¹⁸FDG uptake on positron emission tomography (PET)/computed tomography (CT) as an independent cardiovascular risk factor in patients at high risk for cardiovascular events. We compared 31 consecutive cancer patients presenting with visually enhanced ¹⁸FDG uptake in arterial walls on PET/CT (Group 1) to a selection of 34 matched cancer patients not showing arterial uptake (Group 2). All patients were followed for two years before and six months after PET/CT… Cardiovascular events were classified as older (>6 months before PET/CT) or recent (<6 months before or after PET/CT). ¹⁸FDG uptake was computed on non-attenuation corrected data by a AW/L ratio: mean Arterial Wall uptake/Lung uptake in a normal area, and by SUV on corrected data. A calcium score (CS) was also calculated. ¹⁸FDG uptake and CS were higher in Group 1 than Group 2 (both p = 0.02), and older and recent cardiovascular events were significantly more frequent in Group 1 than Group 2 (p = 0.001 and p = 0.03, respectively). Among the following parameters: number of conventional risk factor, calcium score and presence of ¹⁸FDG uptake, only the latter was significantly related to the occurrence of a recent event by multivariate analysis (p = 0.02). Patients with elevated arterial ¹⁸FDG uptake have a high risk of immediate or future cardiovascular events. Arterial ¹⁸FDG uptake is an indicator of evolving atherosclerotic process and can indicate future cardiovascular events.     

Methylotrophic growth of a mutant strain of the acetogenic bacterium Eubacterium limosum that uses acetate as co-substrate in the absence of CO2

Abstract Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomycin-treated mouse large intestine. E. coli F-18Col⁻, a derivative of E. coli F-18 which no longer makes the E. coli F-18 colicin, colonizes the large intestine as well as E. coli F-18 when fed to mice alone but is eliminated when fed together with E. coli F-18. Recently we randomly cloned E. coli F-18 DNA into E. coli F-18Col⁻ and let the mouse intestine select the best colonizer. In this way, we isolated a 6.5-kb E. coli F-18 DNA sequence that simultaneously stimulated synthesis of type 1 fimbriae and enhanced E. coli F-18Col⁻ colonizing ability. In the present investigation we show that the gene responsible for stimulation of type 1 fimbriae synthesis appears to be leuX , which encodes a tRNA specific for the rare leucine codon UUG. Moreover, it appears that expression of leuX may be regulated by two proteins (22 kDa and 26 kDa) encoded by genes immediately adjacent to leuX .     

肺部病灶~（18）F-FDG PET-CT显像与CT引导下穿刺活检结果对比分析

目的：探讨不同大小病灶18F-FDG PET-CT的显像特点与同层面CT引导下穿刺活检结果的关系。方法：回顾性研究经过18F-FDG PET-CT及CT引导下穿刺活检两种检查的病例,通过统计病灶的大小、病理、穿刺取材部位的放射性浓聚程度、SUVmax来分析不同大小病灶18F-FDG PET-CT的显像特点与同层面CT引导下穿刺活检结果的关系。结果：69例患者,共穿刺74个病灶,71个病灶测得SUVmax,放射性浓聚程度不同的病灶其穿刺敏感性、病灶大小的分布情况有显著性差异（P〈0.05）,≤3 cm组病灶放射性均匀浓聚率高,≥5 cm组放射性均匀浓聚率低（P〈0.05）,≤3 cm的均匀浓聚的恶性病灶其SUVmax低于〉3 cm组（P〈0.05）,良恶性病灶SUVmax无显著性差异（P〉0.05）。结论：不同大小的病灶在18F-FDG PET-CT上放射性浓聚程度不同,反映了病灶生物学特性的空间差异,进而影响穿刺活检的准确率。     

Predicting efficacy of photodynamic therapy by real-time FDG-PET in a mouse tumour model

Dynamic positron emission tomography (PET) combined with the constant infusion of 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) as a tracer permits real-time monitoring of systemic transient metabolic changes resulting from photodynamic therapy (PDT) in tumour bearing animals. The effect of PDT on tumour FDG uptake rates was evaluated using four different sulfonated phthalocyanine analogs as photosensitizers (PS) in combination with either continuous or fractionated illumination protocols. Mice bearing two EMT-6 tumours were infused with FDG to start PDT 30 min later. Dynamic images were acquired to produce FDG uptake over time for the treated and reference tumours. Practically all PDT protocols induced a reduction in the FDG uptake rates in the treated tumour during PDT, except for the zinc tetrasulfophthalocyanine, when using fractionated light, reflecting the low photodynamic efficacy of this PS. In general, the response to PDT was characterized by a rebound in the FDG uptake rate after illumination. A strong drop in FDG tumour uptake rates during PDT, followed by a strong rebound, together with short delay-to-response times, corresponded to optimal long-term tumour response outcomes. This dynamic FDG-PET protocol provides real-time observations to predict long-term PDT efficacy, while using fewer animals than conventional methods, thus making possible the rapid optimization of treatment parameters.     

Rabbit hindlimb glucose uptake assessed with positron-emitting fluorodeoxyglucose

The feasibility of estimating skeletal muscle glucose uptake in vivo was examined by using the glucose analogue 2-[18F]deoxy-2-fluoro-D-glucose (2-[18F]FDG) in the rabbit hindlimb. A pair of collimated coincidence gamma photon detectors was used to monitor the accumulation of tracer in the tissue after 2-[18F]FDG injection. Time-activity curves were generated on a second-by-second basis under control conditions, during increased contractile activity, or hyperinsulinemia. The arterial input of 2-[18F]FDG, plasma glucose, lactate, free fatty acids, and insulin were determined. A graphical (Patlak plot) procedure was used to determine the fractional rate of tracer phosphorylation and therefore trapping in the muscle. From the graphical analysis, the estimated rate of glucose phosphorylation (R) in the unperturbed state was calculated to be 0.037 mumol.min-1.ml-1 of tissue. During perturbation by electrical stimulation, an increase in the rate of tracer phosphorylation (K) was observed. No change in the rate of tracer phosphorylation was observed during hyperinsulinemia. The results support the use of 2-[18F]FDG and the graphical procedure for the noninvasive assessment of glucose uptake by skeletal muscle in vivo. The method described is sensitive to changes in the rate of tracer uptake with respect to time and physiological interventions.     

Synthesis and biological evaluation of novel F-18 labeled pyrazolo[1,5-a]pyrimidine derivatives: potential PET imaging agents for tumor detection

Two novel pyrazolo[1,5-a]pyrimidine derivatives, 7-(2-[¹⁸F]fluoroethylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carbonitrile ([¹⁸F]FEMPPC, [¹⁸F]1) and N-(2-(3-cyano-5-methylpyrazolo[1,5-a]pyrimidin-7-ylamino)ethyl)-2-[¹⁸F]fluoro-4-nitrobenzamide ([¹⁸F]FCMPPN, [¹⁸F]2), have been designed and successively labeled with ¹⁸F by the nucleophilic substitution employing tosylate and nitryl as leaving groups, respectively. The radiochemical synthesis of both compounds was completed within 60 min with final high-performance liquid chromatography purification included. The corresponding radiochemical yields (without decay correction) were approximately 35% and 30%, respectively. Meanwhile, we compared the uptake characteristics of [¹⁸F]1 and [¹⁸F]2 with those of [¹⁸F]FDG and L-[¹⁸F]FET in S180 tumor cells. Furthermore, the tumor uptake of [¹⁸F]1 and [¹⁸F]2 was assessed in mice bearing S180 tumor and compared with [¹⁸F]FDG and L-[¹⁸F]FET in the same animal model. In vitro cell uptake studies showed [¹⁸F]1 had higher uptake than [¹⁸F]FDG, [¹⁸F]2 and L-[¹⁸F]FET over the 2 h period. In ex vivo biodistribution showed tumor/brain uptake ratios of [¹⁸F]2 were 12.35, 10.44, 8.69 and 5.13 at 15 min, 30 min, 60 min and 120 min post-injection, much higher than those of L-[¹⁸F]FET (2.43, 2.54, 2.93 and 2.95) and [¹⁸F]FDG (0.59, 0.61, 1.02 and 1.33) at the same time point. What’s more, the uptake of [¹⁸F]1 in tumor was 1.88, 4.37, 5.51, 2.95 and 2.88 at 5 min, 15 min, 30 min, 60 min and 120 min post-injection, respectively. There was a remarkable increasing trend before 30 min. The same trend was present for L-[¹⁸F]FET before 30 min and [¹⁸F]FDG before 60 min. Additionally, the tumor/brain uptake ratios of [¹⁸F]1 were superior to those of [¹⁸F]FDG at all the selected time points, the tumor/muscle and tumor/blood uptake ratios of [¹⁸F]1 at 30 min were higher than those of L-[¹⁸F]FET at the same time point. MicroPET image of [¹⁸F]1 administered into S180 tumor-bearing mouse acquired at 30 min post-injection illustrated that the uptake in S180 tumor was obvious. These results suggest that compound [¹⁸F]1 could be a new probe for PET tumor imaging.