Evaluation of Tracer Kinetic Models for Analysis of [18F]FDDNP Studies

Purpose  Different pharmacokinetic methods for [¹⁸F]FDDNP studies were evaluated using both simulations and clinical data. Procedures  Methods included two-tissue reversible plasma (2T4k), simplified reference tissue input (SRTM), and a modified 2T4k models. The latter included an additional compartment for metabolites (2T1M). For plasma input models, binding potential, BP_ND, was obtained both directly (=k ₃/k ₄) and indirectly (using volume of distribution ratios). Results  For clinical data, 2T1M was preferred over 2T4k according to Akaike criterion. Indirect BP_ND using 2T1M correlated better with SRTM then direct BP_ND. Fairly constant volume of distribution of metabolites was found across brain and across subjects, which was strongly related to bias in BP_ND obtained from SRTM as seen in simulations. Furthermore, in simulations, SRTM showed constant bias with best precision if metabolites entered brain. Conclusions  SRTM is the method of choice for quantitative analysis of [¹⁸F]FDDNP even if it is unclear whether labeled metabolites enter the brain.     

18F-FDG PET-CT影像表现与非小细胞肺癌预后的关系

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)2-deoxy-¹⁸F-fluoro-D-glucose(¹⁸F-FDG)PET(Positron Emission Tomography)-CT(computerized tomography)的标准摄取值(standarized uptake value,SUV)与预后的关系。方法 选择行¹⁸F-FDG PET-CT扫描并经手术证实的NSCLC患者33例,测定原发病灶的最大SUV,结合临床病理特点,分析SUV与患者生存时间的关系。结果 33例NSCLC病例 PET-CT的平均最大标准摄取值(SUVmax)为10.5±5.4,SUVmax ＜11与SUVmax ≥11病例组的中位生存时间分别为33±0.6个月和27±1.3个月,两组的生存时间有统计学差异(P=0.013),相关分析显示SUVmax 与生存时间呈显著负相关(r=0.8,P=0.008)。单因素分析显示SUVmax与年龄、性别、病理分级、TNM分期及淋巴结转移无明显相关性,SUVmax与病理类型(鳞癌和腺癌)(r=0.348,P=0.048)及临床分型(中心型和周围型)(r=0.379,P=0.029)有关。结论 PET-CT的半定量指标SUV与NSCLC预后呈负相关,SUV对评价非小细胞肺癌预后具有一定的临床意义。     

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.     

Clinical,laboratory and imaging findings in Castleman's disease – The subtype decides

Castleman's disease (CD) is a rare lymphoproliferative disorder with its distinct unicentric (uCD) and multicentric (mCD) entities. The present work aimed at characterizing CD in more detail. From the 775 articles found by a PubMed search, 1133 cases were extracted. Two own cases were included. UCD was identified in 719 (42% males) and mCD in 416 (63% males) cases. Age in uCD was 34 ± 17 and in mCD 48 ± 18 years. The hyaline-vascular type predominated in uCD and the plasma cell type in mCD. Clinical symptoms were more common in mCD. The head and neck region was most frequently affected in uCD and the axillary region in mCD. Prevalence of human immunodeficiency virus (HIV) and human herpesvirus-8 (HHV-8) positivity was higher in mCD. In CT scans, high contrast enhancement and calcifications were more frequent in uCD (all p < 0.0001).The two forms of CD not only differ markedly in their clinical, laboratory and imaging findings, but also in treatment response and prognosis.     

Brain energization in response to deep brain stimulation of subthalamic nuclei in Parkinson's disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment in a subgroup of medically refractory patients with Parkinson''s disease (PD). Here, we compared resting-state ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography images in the stimulator off (DBS_OFF) and on (DBS_ON) conditions in eight PD patients in an unmedicated state, on average 2 years after bilateral electrode implantation. Global standardized uptake value (SUV) significantly increased by ∼11% in response to STN-DBS. To avoid any bias in the voxel-based analysis comparing DBS_ON and DBS_OFF conditions, individual scan intensity was scaled to a region where FDG-SUV did not differ significantly between conditions. The resulting FDG-SUV ratio (FDG-SUVR) was found to increase in many regions in response to STN-DBS including the target area of surgery, caudate nuclei, primary sensorimotor, and associative cortices. Contrary to previous studies, we could not find any regional decrease in FDG-SUVR. These findings were indirectly supported by comparing the extent of areas with depressed FDG-SUVR in DBS_OFF and DBS_ON relatively to 10 normal controls. Altogether, these novel results support the prediction that the effect of STN-DBS on brain activity in PD is unidirectional and consists in an increase in many subcortical and cortical regions.     

FDG-positron emission tomography/computed tomography and standardized uptake value in the primary diagnosis and staging of hilar cholangiocarcinoma

Background

The diagnosis and staging of hilar cholangiocarcinoma (HCCA) remain challenging despite recent advances in imaging. Little is known about the use of positron emission tomography/computed tomography (PET/CT) in HCCA.

Objectives

This study aimed to evaluate the additional value of FDG-PET/CT and standardized uptake value (SUV) in patients with highly suspected HCCA.

Methods

Between February 2006 and August 2009, PET/CT was performed in 30 patients with highly suspected HCCA, all of whom were deemed resectable by conventional staging methods, including laparoscopy. The results of PET-CT and SUV were compared with intraoperative and histopathological findings.

Results

The primary tumour was ¹⁸F-FDG-positive in 88% of patients. Sensitivity and specificity for the detection of regional lymph node metastases and distant metastases were 67% and 68%, and 33% and 96%, respectively. The median SUV in the primary tumour was significantly (P < 0.05) higher in patients with (mean: 8.9) than without (mean: 6.1) distant metastases. The SUV in patients with benign disease (n = 4) showed a trend towards lower values than in patients with cholangiocarcinoma, although this was not significant.

Conclusions

After conventional staging including diagnostic laparoscopy, the additional value of PET/CT is limited. This somewhat disappointing finding may reflect the fact that extensive staging studies were carried out prior to PET/CT. The SUV potentially predicts patients with distant metastases and may differentiate between HCCA and benign lesions that mimic malignancies.