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。这种类型的研究有广泛的应用。这些放射性标记白细胞迁移研究最常见的用途是在未通过其他非侵入性研究明确诊断的疑似感染病例中进行脓肿定位。在这些病例中，自体或异体粒细胞，通过简单的静脉穿刺或单采收集，标记为每公斤患者体重111-铟50 uCi，总不超过500 uCi。在过去的8年里，我们对临床中心不同方案的患者进行了23项脓肿定位研究。在这23例患者中，有3例检测结果呈阳性，并接受了适当的治疗：治疗伴有HIV感染的血友病患者的沙门氏菌骨髓炎，治疗伴有再生障碍性贫血患者的葡萄球菌肺炎，以及治疗伴有佐林格-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。23项铟标记同种异体白细胞研究中有3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，第二项是为了确认没有贩运同种异体免疫受体，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或防止探查性剖腹探查时终止粒细胞输注过程。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素瘤活性的自体克隆T细胞的研究显示，在14名患者中，没有发现任何转移到肿瘤部位的现象。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，并将测试在输注自体克隆T细胞之前使用高度免疫抑制条件的改进方法。运送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 count-ing of blood samples. This type of study has widespread applications. The most common use of these radiolabeled leukocyte trafficking studies is for abscess localization in cases of sus-pected infection not definitively diagnosed by other noninvasive studies. In these cases, auto-logous 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-three studies localizing abscess were performed in Clinical Center patients enrolled in a variety of protocols in the past 8 years. Of these 23, 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 23 Indium-labeled allogeneic leukocyte studies were performed in patients with chronic granulomatous disease, in one case to document clearance of pulmonary infection, in the second to confirm lack of trafficking in an alloimmunized reci-pient, and in the third to localize a cause for fever. In all three cases, gamma imaging results were used to guide therapy, specifically 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 antimelanoma 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 antimelanoma 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.