FLT AS AN IMAGING AGENT FOR DETECTION OF HIV INFECTED TISSUES

FLT 作为检测 HIV 感染组织的显像剂

• 批准号: 6116349
• 负责人: DAVID M ANDERSON
• 金额: $ 8.67万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116349
• 关键词: AIDS; Mammalia; Primates; bioimaging /biomedical imaging; biological products; immunology; infection; inflammation; lymphatic system; model design /development; positron emission tomography; sexually transmitted diseases; virus; AIDS; Mammalia; Primates; bioimaging /biomedical imaging; biological products; immunology; infection; inflammation; lymphatic system; model design /development; positron emission tomography; sexually transmitted diseases; virus

HIV-1 infection is often monitored by measuring the levels of plasma viremia; however, this information does not correlate to the levels of virus detected in other compartments of the body. These reservoirs of virus include follicular dendritic cells, lymphocytes, and macrophages, and may also include thymus, bone marrow, and the central nervous system. Currently the only techniques available for evaluating the presence of HIV are invasive and require specialized processing techniques such as in situ hybridization, which is available only in research laboratories. In this project we used a deoxyfluorothymidine (FLT) combined with a radioactive marker (18F) as an imaging agent with positron emission tomography (PET) scanning to identify tissues that are sites of HIV replication. The radioactivity produced by this agent has a half-life of 2 hours, and the radiation exposure of the tissues is well within the limits experienced by patients injected with radiotherapeutics for clinical use. Four M. nemestrina were assigned to this project, two uninfected controls and two infected with HIV-2. The scanning images appear to highlight areas of lymphoid tissues in the infected macaques as well as other sites of apparent high mitotic activity, possibly indicating sites of virus replication. These encouraging results indicate that more study is warranted.

通常通过测量血浆病毒血症的水平来监测HIV-1感染。但是，此信息与人体其他隔室中检测到的病毒水平无关。 这些病毒的储层包括卵泡树突状细胞，淋巴细胞和巨噬细胞，还可能包括胸腺，骨髓和中枢神经系统。 目前，用于评估HIV存在的唯一技术是侵入性的，需要专门的加工技术，例如原位杂交，仅在研究实验室中可用。 在这个项目中，我们使用了与放射性标记（18F）相结合的脱氧氟氨甲酰胺（FLT）作为具有正电子发射断层扫描（PET）扫描的成像剂，以识别是HIV复制部位的组织。 该药物产生的放射性的半衰期为2小时，组织的辐射暴露在临床用途的患者经历的限制范围内。 将四个N. Nemestrina分配到该项目，两个未感染的对照和两个感染了HIV-2。 扫描图像似乎突出了感染猕猴以及其他明显高丝分裂活性的部位的淋巴组织区域，可能表明病毒复制位置。 这些令人鼓舞的结果表明，有必要进行更多的研究。