Molecular imaging of cancer with copper-64 radiopharmaceuticals and positron emission tomography (PET).
Molecular imaging of cancer with copper-64 radiopharmaceuticals and positron emission tomography (PET).
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DOI：
10.1021/ar800255q
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发表时间：
2009-07-21
影响因子：
18.3
通讯作者：
Anderson CJ
中科院分区：
文献类型：
--
作者：
Shokeen M;Anderson CJ
在过去的几年中，分子成像已经发展成为诊断、理解和监测疾病的重要工具。分子成像是一个跨学科的领域，涉及化学、生物学、物理学和医学领域。跨学科的推动力导致了更灵敏的成像仪器，强大和更安全的放射性药物的发展取得了重大成就，从而提供了更多的选择，以满足个性化的医疗需求。分子成像在癌症研究等领域取得了稳步进展。癌症是一种具有挑战性的疾病，其特征在于异质性、不受控制的细胞分裂以及癌细胞侵入其他组织的能力。分子成像通过积极识别和研究关键的癌症特异性生物标志物（如生长因子受体、蛋白激酶、细胞粘附分子、蛋白酶）以及生物过程（如缺氧、细胞凋亡和血管生成）来应对这些挑战。正电子发射断层扫描（PET）已成为美国临床医生广泛使用的诊断分子成像工具。已经开发并频繁使用了能够对啮齿动物成像并以非侵入性方式生成分辨率低至1 mm的重建图像的小动物PET系统，这反过来又促进了放射性药物开发和药物发现。目前，[18F]标记的2-氟脱氧葡萄糖（FDG）是唯一用于常规临床评价的PET放射性示踪剂，主要用于肿瘤成像。由于生产和可用性的增加，现在对非传统的正电子发射放射性核素，特别是用于PET成像的过渡金属放射性核素的兴趣越来越大。目前正在对铜基放射性核素进行广泛评价，因为它们提供不同范围的半衰期和正电子能量。例如，64 Cu的半衰期（12.7 h）和衰变特性（β+，0.653 MeV [17.8%]; β−，0.579 MeV [38.4%]）使其成为PET成像（β+）和放射治疗（β−）的理想放射性同位素。此外，铜的良好建立的配位化学允许其与多种螯合剂系统反应，所述螯合剂系统可以潜在地连接到抗体、蛋白质、肽和其他生物学相关分子。具有更高体内稳定性的新螯合剂，例如四氮杂大环TETA（1，4，8，11-四氮杂环十四烷-1，4，8，11-四乙酸）的交联（CB）形式，现在是可获得的。最后，成功成像的主要方面之一是在细胞和亚细胞水平上鉴定和表征相关疾病生物标志物，以及对靶标高度特异性的靶向部分。本报告将讨论一些关键癌症生物标志物（如表皮生长因子受体（EGFR）、生长抑素受体（SSR）和整合素α v β 3（αvβ3））与新的和改进的64 Cu放射性药物的PET成像的具体示例。
Molecular imaging has evolved over the past several years into an important tool for diagnosing, understanding, and the monitoring of disease. Molecular imaging has distinguished itself as an interdisciplinary field with contributions from the areas of chemistry, biology, physics and medicine. The cross-disciplinary impetus has led to significant achievements in the development of more sensitive imaging instruments, robust and safer radiopharmaceuticals, thereby providing more choices to fit the personalized medical needs. Molecular imaging is making steadfast progress in the field of cancer research among others. Cancer is a challenging disease, characterized by heterogeneity, uncontrolled cell division, and the ability of cancer cells to invade other tissues. Molecular imaging is addressing these challenges by aggressively identifying and studying key cancer-specific biomarkers such as growth factor receptors, protein kinases, cell adhesion molecules, proteases, as well as biological processes such as hypoxia, apoptosis, and angiogenesis. Positron emission tomography (PET) has become a widely used diagnostic molecular imaging tool by clinicians in the United States. Small animal PET systems that can image rodents and generate reconstructed images in a non-invasive manner with a resolution as low as 1 mm have been developed and used frequently, which in turn facilitate radiopharmaceutical development and drug discovery. Currently, [18F]-labeled 2-fluorodeoxyglucose (FDG) is the only PET radiotracer used for routine clinical evaluation, primarily for oncological imaging. There is now increasing interest in non-traditional positron-emitting radionuclides, particularly those of the transition metals for imaging with PET because of increased production and availability. Copper based radionuclides are currently being extensively evaluated as they offer a varying range of half-lives and positron energies. For example, the half-life (12.7 h) and decay properties (β+, 0.653 MeV [17.8 %]; β−, 0.579 MeV [38.4 %]) of 64Cu make it an ideal radioisotope for PET imaging (β+) and radiotherapy (β−). In addition, the well established coordination chemistry of copper allows for its reaction with a wide variety of chelator systems that can potentially be linked to antibodies, proteins, peptides and other biologically relevant molecules. New chelators with greater in vivo stability, such as the cross bridged (CB) versions of tetraazamacrocyclic TETA (1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid), are now available. Finally, one of the major aspects of successful imaging is the identification and characterization of a relevant disease biomarker at the cellular and sub-cellular level, and a targeting moiety highly specific for the target. This account will discuss specific examples of PET imaging of some of the key cancer biomarkers such as epidermal growth-factor receptor (EGFR), somatostatin receptors (SSRs), and integrin alpha v beta 3 (αvβ3) with new and improved 64Cu based radiopharmaceuticals.
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影响因子：
6.1
作者：
BAUER, W;BRINER, U;PLESS, J
通讯作者：
PLESS, J
影响因子：
4
作者：
Heroux, Katie J.;Woodin, Katrina S.;Rheingold, Arnold L.
通讯作者：
Rheingold, Arnold L.
DOI：
10.1007/s002590050064
发表时间：
1997-04-01
期刊：
EUROPEAN JOURNAL OF NUCLEAR MEDICINE
影响因子：
--
作者：
deJong, M;Bakker, WH;Macke, HR
通讯作者：
Macke, HR
影响因子：
7.3
作者：
Boswell, CA;Sun, XK;Anderson, CJ
通讯作者：
Anderson, CJ
影响因子：
3.4
作者：
Li, Wen Ping;Meyer, Laura A.;Anderson, Carolyn J.
通讯作者：
Anderson, Carolyn J.