Kinetic Studies Of Indium-labeled Leukocytes

铟标记白细胞的动力学研究

• 批准号: 6546520
• 负责人: SUSAN F LEITMAN-KLINMAN
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6546520
• 关键词: bioimaging /biomedical imaging; blood tests; cell migration; cell population study; clinical trials; diagnosis design /evaluation; human subject; human therapy evaluation; indium; inflammation; leukapheresis; leukocytes; melanoma; neoplasm /cancer radiation therapy; patient care management; patient oriented research; radiodiagnosis; radionuclide imaging /scanning; radionuclide therapy; radiotracer; scintillation cameras; scintillation counter

The kinetic patterns of fresh, frozen-thawed, or cultured human leukocytes are studied by tagging the cells ex vivo with 111-Indium, a radioisotopic label, and measuring their distribution throughout the body by means of gamma camera imaging and gamma counting of blood samples. The most common use of radiolabeled leukocyte trafficking studies is for abscess localization in cases of suspected infection not definitively diagnosed by other non-invasive studies. In these cases, autologous or allogeneic granulocytes, collected by simple phlebotomy or by apheresis, are labeled with 50 uCi of 111-Indium per kg of patient weight, not to exceed 500 uCi total. Twenty-four studies for the purpose of localizing abscess were performed in Clinical Center patients enrolled in a variety of protocols in the past 9 years. Of these 24, three were positive and received appropriate therapy for salmonella osteomyelitis in a hemophiliac patient with HIV infection, staphylococcal pneumonia in a patient with aplastic anemia, and diverticular abscess in a patient with Zollinger-Ellison syndrome. In many of the negative studies, unnecessary surgical exploration was avoided. Three of the 24 indium-labeled allogeneic leukocyte studies were performed in patients with chronic granlomatous disease, in one case to document clearance of pulmonary infection, in the second to confirm lack of trafficking in an alloimmunized recipient, and in the third to localize a cause for fever. In all three cases, gamma imaging results were used to guide therapy, in specific, to terminate a course of granulocyte transfusions when they were either no longer necessary or were ineffective, or to prevent an exploratory laparotomy. Collaborative trials with the Surgery Branch, NCI, have investigated the diagnostic utility and prognostic application of radiolabeled autologous tumor infiltrating lymphocyte (TIL) studies in patients with metastatic melanoma. TIL trafficking studies revealed metastatic deposits that were undetected clinically, and TIL trafficking to sites of tumor was strongly correlated with tumor regression following TIL infusion. In contrast, studies of indium-labeled autologous, cloned T-cells with anti-melanoma activity did not show any trafficking to tumor sites in 14 patients. The results of the trafficking studies were highly predictive of clinical response, in that none of the 14 patients had regression of disease in response to the cloned anti-melanoma T-cells. On the basis of these studies, the protocol was terminated, and a modified approach, using highly immunosuppressive conditioning prior to infusion of autologous cloned T-cells, will be tested. Trafficking of indium-labeled autologous cells will be used as one of the benchmarks with which to evaluate the response to therapy.

通过用放射性同位素标记物111-铟离体标记细胞，并通过γ照相机成像和血液样品的γ计数来测量它们在整个身体中的分布，来研究新鲜的、冻融的或培养的人白细胞的动力学模式。放射性标记的白细胞运输研究最常见的用途是在其他非侵入性研究无法明确诊断的疑似感染病例中进行脓肿定位。在这些情况下，通过简单的静脉切开术或单采术收集的自体或同种异体粒细胞用50 uCi的111-铟/kg患者体重标记，总计不超过500 uCi。在过去9年中，在入组各种方案的临床中心患者中进行了24项旨在定位脓肿的研究。在这24例患者中，3例为阳性，并接受了适当的治疗，分别为血友病合并HIV感染患者的盐性骨髓炎、再生障碍性贫血患者的葡萄球菌肺炎和Zollinger-Ellison综合征患者的憩室脓肿。在许多阴性研究中，避免了不必要的手术探查。在24项铟标记的同种异体白细胞研究中，有3项是在慢性肉芽肿病患者中进行的，其中1项是为了记录肺部感染的清除情况，第2项是为了确认同种免疫受体中缺乏运输，第3项是为了定位发热原因。在所有3例病例中，伽马成像结果用于指导治疗，具体而言，用于在不再需要或无效时终止粒细胞输注过程，或用于防止剖腹探查术。与NCI外科分支的合作试验研究了放射性标记的自体肿瘤浸润淋巴细胞（TIL）研究在转移性黑色素瘤患者中的诊断效用和预后应用。TIL运输研究揭示了临床上未检测到的转移性沉积，并且TIL运输至肿瘤部位与TIL输注后的肿瘤消退密切相关。相比之下，对具有抗黑色素瘤活性的铟标记自体克隆T细胞的研究在14名患者中未显示任何向肿瘤部位的运输。运输研究的结果高度预测了临床反应，因为14名患者中没有一名对克隆的抗黑色素瘤T细胞有反应的疾病消退。在这些研究的基础上，终止了该方案，并将测试在输注自体克隆T细胞之前使用高度免疫抑制调节的改良方法。铟标记的自体细胞的运输将被用作评价治疗反应的基准之一。