放射性标记氨基酸的肿瘤基础研究

随着代谢显像的不断发展，放射性标记氨基酸引起临床更多关注。弄清氨基酸代谢基础和标记氨基酸在肿瘤中的作用更显必要。目前临床最常用的氨基酸为像剂如^11C-蛋氨酸，^11C-酪氨酸和^123I－碘代甲基酪氨酸等，与^18F－FDG PET相比很少受炎症影响，对脑部肿瘤显像准确性更好，对其他类型肿瘤也显示出更多的临床意义。     

用于肿瘤代谢显像的几种放射性标记氨基酸

随着代谢显像的广泛应用,放射性标记氨基酸越来越引起临床关注。与18F-FDGPET显像相比,氨基酸显像的优点在于其受炎症的影响较小。对于脑肿瘤,氨基酸代谢显像具有较高的诊断价值。对大多数其它类型的肿瘤而言,尽管凭现有资料尚不能得出最终结论,但其总体可行性已得到充分显示。因此,仍有必要进行经过精心设计的更大样本病例的研究。本文着重描述了11C-蛋氨酸(MET)、11C-酪氨酸(TYR)、123I-甲基酪氨酸(IMT)的基本特性和临床应用。     

用于肿瘤代谢显像的几种放射性标记氨基酸

随着代谢显像的广泛应用，放射标记氨基酸越来越引起临床关注。与^18F-FDG PET显像相比，氨基酸显像的优点在于其受炎症的影响较小，对于脑肿瘤，氨基酸代谢显像具有较高的诊断价值。对大多数其它类型的肿瘤而言，尽管凭现有资料尚不能得出最终结论，但其总体可行性巳得到充分显示。因此，仍有必要进行经过精心设计的更大样本病例的研究。本着重描述了^11G-蛋氨酸（NET）、^11G-酪氨酸（TYR）、^123I-甲基酪氨酸（IMT）的基本特性的临床应用。     

11C-胆碱PET在前列腺癌中的临床应用探讨

前列腺癌是老年男性的常见恶性肿瘤,但是常规显像困难.11C-胆碱是新近研究较多的一种正电子肿瘤阳性显像剂,因它不通过泌尿系统排泄而被用于前列腺癌的临床诊断中.通过11C-胆碱、18F-氟脱氧葡萄糖、11C-乙酸和11C-甲硫氨酸在前列腺癌PET结果的比较,总结了11C-胆碱PET在前列腺癌的临床应用近况.     

11C标记的放射性药物在PET-CT肿瘤诊断上的应用

18F-氟代脱氧葡萄糖（18F-FDG）是目前最常用的肿瘤诊断药物,但由于其正常的生理分布,影响了一些肿瘤的诊断.本文主要介绍了11C标记的正电子药物：11C-甲硫氨酸、11C-胆碱、11C-乙酸盐在原发脑肿瘤、头颈部肿瘤、肺癌、肝癌、妇科肿瘤、前列腺癌、膀胱癌、骨及软组织肿瘤上诊断及分期、疗效监测的价值.研究表明,11C标记的肿瘤正电子药物是18F-FDG的一个重要补充.     

^11C-胆碱PET显像的临床初步应用

目的: 初步探讨11C-胆碱PET显像诊断体内占位病变的良恶性价值.材料和方法: 对3例脑内、14例肺内占位病变患者同时行N-甲基-11C胆碱(11C-胆碱)和18F-FDG PET显像,ROI方法测定最大标准摄取值(SUVmax).结果: 13处恶性占位病灶11C-胆碱PET显像均为阳性;但病灶大小与SUVmax间无明显相关性.8处良性占位病灶,18F-FDG均为假阳性,11C-胆碱PET显像仅有1例为假阳性.11C -胆碱显像漏检1处肺癌肾上腺转移病灶.结论: 11C-胆碱PET显像可能成为肿瘤良恶性鉴别的可靠方法.     

11C标记的放射性药物在PET-CT肿瘤诊断上的应用

18F-氟代脱氧葡萄糖(18F-FDG)是目前最常用的肿瘤诊断药物,但由于其正常的生理分布,影响了一些肿瘤的诊断。本文主要介绍了11C标记的正电子药物:11C-甲硫氨酸、11C-胆碱、11C-乙酸盐在原发脑肿瘤、头颈部肿瘤、肺癌、肝癌、妇科肿瘤、前列腺癌、膀胱癌、骨及软组织肿瘤上诊断及分期、疗效监测的价值。研究表明,11C标记的肿瘤正电子药物是18F-FDG的一个重要补充。     

11C-胆碱和18F-FDG在肿瘤PET中的比较

11C-胆碱是最近研制的一种正电子肿瘤阳性显像剂,在肿瘤/非靶组织的比值高于18F-FDG,特别在脑肿瘤和前列腺癌显像方面较18F-FDG显示出优势.11C-胆碱和18F-FDG在脑肿瘤、肺癌、食道癌和前列腺癌的诊断方面各有优劣,两者的摄取机理与显像方法也不同.除了11C-胆碱,还有18F-氟代胆碱(18F-fluorocholine),其临床价值有待更多的研究来证实.     

氨基酸类正电子显像在胶质瘤中的研究进展

胶质瘤是神经系统中较常见的疾病之一,严重危害人类健康,其预后取决于分期、手术切除情况、组织学分类、病理分级等。氨基酸类正电子显像剂如11C-蛋氨酸（11C-MET）、18F-酪氨酸（18F-FET）等在胶质瘤PET显像中有较为广泛的应用。11C-MET和18F-FET作为氨基酸类显像剂既可以反映人体内的氨基酸转运、代谢和蛋白质合成,又可以对胶质瘤进行早期诊断、分级、鉴别坏死与复发、放疗靶区的勾画及判断预后等,对其临床诊疗有较大的价值。笔者就两种氨基酸类显像剂在胶质瘤中的应用现状进行综述。     

O—（2—^18F—氟代乙基）—L—酪氨酸的合成及初步动物实验

目的 研制了^18F标记的氨基酸类肿瘤显像剂O-(2-^18F-氟代乙基）－L－酪氨酸（^18F-FET)。方法 亲核氟代法制备2－^18F-氟代乙醇对甲苯磺酸酯，再与酪氨酸二钠反应得^18F-FET。进行了小鼠体内分布实验和小鼠肿瘤显像。结果 ^18-FET放化收率4．4％，放化纯度＞99％。注射后60min小鼠肿瘤显像清晰，结论 ^18F-FET标记简便，小中瘤显像清晰。     

Radiolabeled amino acids: basic aspects and clinical applications in oncology.

As the applications of metabolic imaging are expanding, radiolabeled amino acids may gain increased clinical interest. This review first describes the basic aspects of amino acid metabolism, then continues with basic aspects of radiolabeled amino acids, and finally describes clinical applications, with an emphasis on diagnostic value. A special focus is on (11)C-methionine, (11)C-tyrosine, and (123)I-iodomethyltyrosine, because these have been most used clinically, although their common affinity for the L-transport systems may limit generalization to other classes of amino acids. The theoretic and preclinical background of amino acid imaging is sound and supports clinical applications. The fact that amino acid imaging is less influenced by inflammation may be advantageous in comparison with (18)F-FDG PET imaging, although tumor specificity is not absolute. In brain tumor imaging, the use of radiolabeled amino acids is established, the diagnostic accuracy of amino acid imaging seems adequate, and the diagnostic value seems advantageous. The general feasibility of amino acid imaging in other tumor types has sufficiently been shown, but more research is required in larger patient series and in well-defined clinical settings.     

肿瘤血管活性肠肽受体显像

血管活性肠肽(VIP)是一种由28个氨基酸组成具有多种功能的神经递质,能通过其受体调节正常及肿瘤细胞的增殖和分化。VPAC(VIP受体)广泛存在于各种正常和肿瘤组织中,但其在肿瘤组织中的表达密度远大于正常组织,这为放射性核素标记的血管活性肠肽受体显像奠定基础。此种显像已应用于多种肿瘤的诊断、分期、治疗方案选择与预后评价。     

Neuroimaging in brain tumors

Advances in neuroimaging have modified diagnosis, treatment and clinical management of brain tumors. However, neuropathological study remains necessary in order to get the best clinical management. Surgery and radiotherapy planning are imaging-dependent procedures, and MRI is the standard imaging modality for determining precisely tumor location and its anatomical relationship with surrounding brain structures. In high-grade tumors it has been accepted that tumoral areas with contrast uptake in CT, or T1-weighted MRI contrast enhancement corresponds to solid tumor. However, relationship between MRI and invasive tumor areas remains less defined. Therefore, it is generally accepted that conventional MRI is not sufficient to delineate the real extension of brain tumors. In recent years, PET using 18FDG and amino acid radiotracers ((11)C-Methionine, (18)FDOPA, (18)FET) and SPECT with (201-)Thallium, as well as advanced MRI sequences (Perfusion, Diffusion-weighted, Diffusion tensor imaging and tractography), and functional MRI, have added important complementary information in the characterization, therapy planning and recurrence differential diagnosis of brain tumors. In this continuing education review of neuroimaging in brain tumors, technical aspects and clinical applications of different imaging modalities are approached in a multidisciplinary way.     

11C—甲硫氨酸PET在乳腺癌诊疗中的价值

乳腺癌是我国妇女最常见的恶性肿瘤之一,也是妇女中除肺癌外病死率最高的恶性肿瘤,早期诊断是降低乳腺癌病死率的关键因素.目前,乳腺癌的诊断方法主要是钼靶X线乳腺摄影、超声检查、磁共振成像、细针穿刺活组织检查等.乳腺癌的基因变化导致癌肿血流增加,葡萄糖代谢、氨基酸转运、蛋白质合成、受体表达增加,DNA合成和细胞增殖活跃,并诱导细胞凋亡.PET结果显示.肿瘤部位对18F-氟脱氧葡萄糖(18F-FDG)和11C-甲硫氨酸(11C-MET)摄取均增高而11C-MET合成方便快捷,价格较18F-FDG低,其在乳腺癌中的应用价值国外已有诸多报道.     

Pharmacokinetics and tumor retention of 125I-labeled RGD peptide are improved by PEGylation

Tumor growth and metastasis are angiogenesis dependent. Overexpression of integrin alphavbeta3 in angiogenic vessels as well as various malignant human tumors suggests the potential of suitably labeled antagonists of this adhesion receptor for radionuclide imaging and therapy of tumors. Small head-to-tail cyclic peptides including the Arg-Gly-Asp (RGD) amino acid sequence have been radiolabeled and studied in preclinical animal models. However, the fast blood clearance, high kidney and liver uptake, and rapid washout from tumors make this type of tracer ineffective for clinical applications. In this study we modified the cyclic pentapeptide c(RGDyK) with monofunctional methoxy-PEG (mPEG, M.W. = 2,000) and labeled the RGD-mPEG conjugate with 125I. We studied the tumor targeting efficacy and in vivo pharmacokinetic properties of 125I-RGD-mPEG by means of direct tissue sampling and autoradiography in mice xenografted subcutaneously with U87MG glioblastoma. Compared to the 125I-RGD analog, this PEGylated RGD peptide revealed faster blood clearance, lower kidney uptake, and prolonged tumor uptake without compromising the receptor targeting ability.     

Radiolabeled peptides in diagnosis and therapy

During the past few years, there has been exponential growth in the development of radiolabeled peptides for diagnosis and therapy. This is because the peptides can be synthesized easily and inexpensively, they have fast clearance and rapid tissue penetration, and they are less likely to be immunogenic. More importantly, most peptides have a high affinity for characteristic receptor molecules that are overexpressed on malignant mammalian cells. Peptides can be labeled with a variety of radionuclides intended for specific applications, diagnostic or therapeutic, by using both conventional and novel chelating moieties, many of which can be incorporated during the solid state synthesis of a chosen peptide. High specific-activity peptides can be prepared and used to minimize unwanted physiologic effects, and known sequences of amino acids can be modified to slow their in vivo catabolic rate. These characteristics have paved the way for the preparation of a large number of radiolabeled peptides for a variety of clinical and experimental applications. This article briefly discusses the peptide chemistry; it also summarizes the preparation of radiolabeled peptides and outlines their applications in imaging vascular thrombosis, detecting infection and inflammation, and localizing tumors. Their therapeutic applications in oncology are also presented and the future directions outlined. Peptides that have been approved for human use, such as AcuTect (Diatide, Londonderry, NH) or OctreoScan (Mallinckrodt, St. Louis, MO), or those that have made it to clinical trials, are emphasized. Also discussed are selected promising agents that are still in preclinical investigation.     

Preclinical and clinical evaluation of O-[11C]methyl-L-tyrosine for tumor imaging by positron emission tomography

We performed preclinical and clinical studies of O-[11C]methyl-L-tyrosine, a potential tracer for imaging amino acid transport of tumors by positron emission tomography (PET). Examinations of the radiation-absorbed dose by O-[11C]methyl-L-tyrosine and the acute toxicity and mutagenicity of O-methyl-L-tyrosine showed suitability of the tracer for clinical use. The whole-body imaging of monkeys and healthy humans by PET showed low uptake of O-[11C]methyl-L-tyrosine in all normal organs except for the urinary track and bladder, suggesting that the O-[11C]methyl-L-tyrosine PET has the potential for tumor imaging in the whole-body. Finally, the brain tumor imaging was preliminarily demonstrated.     

O-(2-[18F]fluoroethyl)-L-tyrosine: uptake mechanisms and clinical applications

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a promising tracer for PET that has demonstrated convincing results especially in the diagnostics of brain tumors. In contrast to other radiolabeled amino acids, it can be produced with high efficiency and distributed in a satellite concept like the widely used 2-[18F]fluoro-2-deoxy-D-glucose. Although FET is not incorporated into proteins, it shows high uptake in cerebral gliomas and in extracranial squamous cell carcinomas owing to increased transport. The tracer exhibits high in vivo stability, low uptake in inflammatory tissue and suitable uptake kinetics for clinical imaging, which indicates that it may become a new standard tracer for PET. In this article, the present knowledge on the uptake mechanisms and the clinical applications of FET are reviewed and the clinical perspectives are discussed.     

Imaging studies of patients with malignant fibrous histiocytoma using C-11-alpha-aminoisobutyric acid (AIB)

Alpha-aminoisobutyric acid (AIB), a synthetic, nonmetabolized amino acid which is rapidly transported into viable cells by the A-type or alanine-preferring amino acid transport system, has been labeled with the short-lived, positron-emitting radionuclide carbon-11. Carbon-11 labeled AIB is currently being evaluated as a tumor imaging agent for in vivo amino acid transport studies in patients with cancer. In this study, C-11 AIB was used to image two patients with malignant fibrous histiocytoma (MFH), a pleomorphic sarcoma. Following intravenous administration of C-11 AIB, tumors in the distal femur of one patient and in the anterior chest wall of another patient were well visualized using high energy gamma scintigraphy. Since therapy may alter the accumulation of amino acids in tumor tissue, studies using C-11 AIB in patients with MFH before and after chemotherapy are in progress.