PET and drug research and development.

The use of PET to examine the behavioral, therapeutic and toxic properties of drugs and substances of abuse is emerging as a powerful new scientific tool. PET provides a new perspective on drug research by virtue of its ability to directly assess both pharmacokinetic and pharmacodynamic events in humans and in animals. These parameters can be assessed directly in the human body both in healthy volunteers and in patients. Moreover, the new generation of high-resolution, small-animal cameras hold the promise of introducing imaging in the early stages of drug development and make it possible to carry out longitudinal studies in animals and to study genetically altered animals. This places PET in a unique position to contribute significantly to the process of drug development through understanding the molecular mechanisms underlying drug action while addressing some very practical questions such as determining effective drug doses for clinical trials for new drugs, determining the duration of drug action and examining potential drug interactions.     

Guidelines to PET measurements of the target occupancy in the brain for drug development

This guideline summarizes the current view of the European Association of Nuclear Medicine Drug Development Committee. The purpose of this guideline is to guarantee a high standard of PET studies that are aimed at measuring target occupancy in the brain within the framework of development programs of drugs that act within the central nervous system (CNS drugs). This guideline is intended to present information specifically adapted to European practice. The information provided should be applied within the context of local conditions and regulations.     

肿瘤血管生成的PET检测

肿瘤血管生成作为肿瘤的主要特征,在肿瘤生长和转移中起着重要作用,为肿瘤治疗提供了新策略.通过标记血管生成相关的受体、多肽、激酶或细胞外基质蛋白,形成高亲和力的分子探针,与肿瘤血管生成过程中产生的特异性靶分子结合,从而显示包括整合素、VEGF/VEGFR、基质金属蛋白酶(MMPs)等与血管生成关系密切的特征性血管生成因子,可从分子水平对肿瘤新生血管及血管靶向治疗疗效进行无创性检测.笔者就肿瘤血管生成PET影像学检测研究进展及未来发展作一综述.     

Animal models for the study of tendinopathy

Tendinopathy is a common and significant clinical problem characterised by activity-related pain, focal tendon tenderness and intratendinous imaging changes. Recent histopathological studies have indicated the underlying pathology to be one of tendinosis (degeneration) as opposed to tendinitis (inflammation). Relatively little is known about tendinosis and its pathogenesis. Contributing to this is an absence of validated animal models of the pathology. Animal models of tendinosis represent potential efficient and effective means of furthering our understanding of human tendinopathy and its underlying pathology. By selecting an appropriate species and introducing known risk factors for tendinopathy in humans, it is possible to develop tendon changes in animal models that are consistent with the human condition. This paper overviews the role of animal models in tendinopathy research by discussing the benefits and development of animal models of tendinosis, highlighting potential outcome measures that may be used in animal tendon research, and reviewing current animal models of tendinosis. It is hoped that with further development of animal models of tendinosis, new strategies for the prevention and treatment of tendinopathy in humans will be generated.     

Serum tumor markers and PET/CT imaging for tumor recurrence detection

When confronted with a suspicious rise in CA 15.3 in asymptomatic breast cancer patients following primary treatment and negative or equivocal conventional imaging findings, FDG PET/CT allows assessment of the site and extent of the recurring disease with an accuracy of 83 %. Both FDG PET and FDG PET/CT are superior when compared to CT alone for the purpose of recurrence detection in patients suffering from ovarian carcinoma who have completed primary therapy but demonstrate a rising serum CA-125 level. As the global accuracy of CT alone for detection of recurrence of ovarian cancer approximates 80 %, CT scan should be performed upfront to identify the site of recurrence. When confronted with negative or equivocal CT findings, FDG PET alone or FDG PET/CT should be added. In patients with rising serum CEA levels that have undergone primary treatment for a colorectal carcinoma, both FDG PET and FDG PET/CT allow detection of tumor recurrence with an accuracy of 95 %, well above that of CT and MRI. Available studies further suggest that FDG/PET findings will affect treatment management in 28–50 % of these patients. The detection rate of both 11C-choline and 18F-choline PET and PET/CT for local, regional, and distant recurrence in prostate carcinoma patients with a biochemical recurrence increases with rising PSA value at the time of imaging and reaches about 75 % in patients with PSA >3 ng/mL. Furthermore, PET and PET/CT with [¹¹C]- and [¹⁸F]-choline derivates may be helpful in the clinical setting for optimization of individualized treatment.     

Animal models of cancer in interventional radiology

Animal models will play an increasingly important role in oncology research, especially for solid tumours such as hepatocellular carcinoma that are resistant to chemotherapy. Many models have been used, but there is a need for increased awareness of the limitations of these models and also a need for guidance for future model development.     

Animal genetic models for complex traits of physical capacity

Animal genetic models for complex traits of physical capacity. Exerc. Sport Sci. Rev., Vol. 29, No. 1, pp 7-14, 2001. Understanding the genetic basis for variance in complex physical traits such as aerobic capacity has become an attainable goal. A starting point is the development or identification of animal genetic models that contrast the low and high values for the trait of interest. Genes that cause natural trait variation can ultimately be determined from animal models via genetic linkage.     

Circulating tumor cells and PET

Understanding the distinct molecular features of solid tumors provides the opportunity to develop more targeted and effective therapies. The evaluation and monitoring of these therapies require sophisticated laboratory and imaging technologies to detect potential benefit not necessarily translating into significant changes in tumor size. PET has emerged as the most sensitive imaging technique for providing the metabolic profile of an individual tumor. Most recently, the detection of circulating tumor cells in the peripheral blood of patients with advanced malignancies has provided another dimension to the use of PET for sensitive therapeutic monitoring. Moreover, molecular characterization of circulating tumor cells holds promise for furthering the care of cancer patients.     

非FDG PET肿瘤显像技术

2-脱氧-2^18F代-D-葡萄糖（^18F-FDG）自1976年被开发以来，因其反映细胞葡萄糖转运、摄取和磷酸化等生物特性而在临床和生物研究中获得越来越广泛的应用。肿瘤细胞的糖代谢机制与正常组织不同，肿瘤细胞的葡萄糖转运mRNA表达增加，葡萄糖转运蛋白Glut1、Glut3和己糖激酶水平升高，葡萄糖-6-磷酸酶水平下调，使肿瘤细胞对FDG的摄取异常增加。因此，90％以上的临床PET肿瘤显像使用^18F-FDG，使之成为核医学工作中无可争议的“辕马（work horse）”。     

Partial-volume effect in PET tumor imaging.

PET has the invaluable advantage of being intrinsically quantitative, enabling accurate measurements of tracer concentrations in vivo. In PET tumor imaging, indices characterizing tumor uptake, such as standardized uptake values, are becoming increasingly important, especially in the context of monitoring the response to therapy. However, when tracer uptake in small tumors is measured, large biases can be introduced by the partial-volume effect (PVE). The purposes of this article are to explain what PVE is and to describe its consequences in PET tumor imaging. The parameters on which PVE depends are reviewed. Actions that can be taken to reduce the errors attributable to PVE are described. Various PVE correction schemes are presented, and their applicability to PET tumor imaging is discussed.     

多示踪剂成像技术在肿瘤诊断方面的应用研究

全球恶性肿瘤发病率和死亡率持续升高,早期诊断对于病人预后及治疗方案的选择至关重要。正电子发射体层成像(PET)目前已广泛用于肿瘤评价,单示踪剂PET成像为最常用的检查方法。由于每种正电子示踪剂仅能反映一种细胞内的信息,在肿瘤诊断应用中易导致假阴性或假阳性诊断,因此需要合理联合应用多种示踪剂来提高PET在肿瘤诊断中的准确性。对多示踪剂PET技术在肿瘤诊断方面的应用作一综述。     

Comparison of dual-head coincidence PET versus ring PET in tumor patients.

This study compared the multiring detector (Ring-PET) and the dual-head coincidence imaging system (DH-PET) for staging/ restaging neoplastic patients before or after surgery or radiochemotherapy. METHODS: Seventy patients with suspected tumor recurrence or metastatic dissemination received an intravenous dose of 18F-fluorodeoxyglucose (FDG) under overnight fasting and were studied in sequence with a dedicated positron emission tomograph with Ring-PET and a DH-PET. Ring-PET studies were performed 45-75 min postinjection and were followed by a DH-PET scan approximately 3 h postinjection. Number and location of the hypermetabolic lesions detected on DH-PET and Ring-PET reconstructed images were blindly assessed by three independent observers. RESULTS: DH-PET identified all 14 head lesions detected by Ring-PET, 53 of 63 thoracic lesions and 36 of 45 abdominal lesions. Of the 19 lesions not identified by DH-PET, 6 were smaller than 10 mm, 8 were between 10 and 15 mm and 1 was 18 mm; dimensions of 4 bone lesions were not available. A concordant restaging, based on location and number of lesions detected, was found in all 14 patients with head tumors, in 28 of 30 patients with thoracic tumors and in 24 of 26 patients with abdominal tumors. CONCLUSION: We found a good agreement between Ring-PET and DH-PET assessment of oncologic patients in detecting hypermetabolic lesions > or = 10-15 mm.     

18F-氟脱氧葡萄糖PET监测实体瘤放化疗疗效的应用进展

利用18^F-氟脱氧葡萄糖（18^F—FDG）PET监测肿瘤放疗或化疗的疗效以及区分残余或复发病灶已广泛用于临床。18^F-FDG PET定量分析肿瘤在治疗开始时的变化可以预测肿瘤对治疗的反应性及患者的预后，并可根据肿瘤的反应性调整治疗方案。利用18^F-FDG PET早期预测肿瘤对放、化疗的反应性，在个体化治疗方案的制定、减少无效治疗所带来的副作用等方面有着巨大的潜能。     

PET及PET-CT在监测肿瘤治疗效果中的价值

18F-氟代脱氧葡萄糖(18F-FDG)PET和PET-CT既能准确鉴别肿瘤残留与纤维化,又能通过定量评价治疗前后18F-FDG摄取的变化来早期预测疗效和评价预后,指导临床及时调整治疗方案,因此越来越多地被用于监测肿瘤放化疗疗效。目前已建立了一些应用PET和PET-CT监测肿瘤疗效的具体方法,研究结果显示,PET及PET-CT在监测肿瘤疗效方面存在明显的优势,但也存在问题。     

胰腺癌动物模型的类型及特点

胰腺癌是常见的恶性肿瘤,恶性程度较高、发展快、预后差。胰腺癌的动物模型是胰腺癌研究的重要组成部分。建立理想的胰腺癌动物模型为研究者探索胰腺癌发病机制、研究预防策略、评价临床疗效提供了适当的方法。常见的胰腺癌动物模型包括化学诱导型、种植型及基因工程型。就各种胰腺癌动物模型的建立方法及特点进行综述。     

胰腺癌动物模型的类型及特点

胰腺癌是常见的恶性肿瘤,恶性程度较高、发展快、预后差。胰腺癌的动物模型是胰腺癌研究的重要组成部分。建立理想的胰腺癌动物模型为研究者探索胰腺癌发病机制、研究预防策略、评价临床疗效提供了适当的方法。常见的胰腺癌动物模型包括化学诱导型、种植型及基因工程型。就各种胰腺癌动物模型的建立方法及特点进行综述。     

FDG PET scan in a primitive neuroectodermal tumor

Primitive peripheral neuroectodermal tumor (PNET) is a rare tumor that often arises in soft tissue. Magnetic resonance imaging is a good diagnostic tool that can establish the extent of disease. The utility of positron emission tomography (PET) using F-18-fluoro-2-deoxy-D-glucose (FDG) in the diagnostic work-up and staging of PNET has not been well established. We present a case of PNET of the right upper extremity that did not show FDG uptake despite its large size and aggressive nature.