Kinetic Studies Of Indium-labeled Leukocytes

通过在体外用111-铟（一种放射性同位素标记）标记细胞，并通过伽马相机成像和血液样本的伽马计数来测量它们在全身的分布，研究了新鲜、冻融或培养的人类白细胞的动力学模式。放射标记白细胞迁移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。在这些病例中，通过简单的静脉穿刺或单采收集的自体或异体粒细胞被标记为每公斤患者体重111-铟的50 uCi，总数不超过500 uCi。在过去的9年里，我们在临床中心的不同方案的患者中进行了24项关于脓肿定位的研究。在这24例患者中，3例呈阳性，并接受了适当的治疗，分别是感染艾滋病毒的血友病患者的沙门氏菌骨髓炎、再生障碍性贫血患者的葡萄球菌肺炎和佐林格-埃里森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项铟标记异基因白细胞研究中，有三项是在慢性肉芽肿性疾病患者中进行的，其中一项是为了记录肺部感染的清除，第二项是为了确认接受同种异体免疫的患者没有贩运，第三项是为了确定发烧的原因。在所有三个病例中，伽马成像结果用于指导治疗，特别是在不再需要或无效时终止粒细胞输注过程，或防止探查性剖腹手术。与NCI外科分会的合作试验研究了放射标记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转运研究揭示了临床未发现的转移沉积，TIL转运到肿瘤部位与TIL输注后肿瘤消退密切相关。相比之下，对铟标记的具有抗黑色素瘤活性的自体克隆t细胞的研究显示，在14名患者中，t细胞没有向肿瘤部位转移。贩运研究的结果高度预测了临床反应，因为14名患者中没有人因克隆的抗黑色素瘤t细胞而出现疾病消退。在这些研究的基础上，该方案被终止，并将测试一种改进的方法，即在输注自体克隆t细胞之前使用高度免疫抑制条件。贩卖铟标记的自体细胞将被用作评估治疗反应的基准之一。

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.