KINETIC STUDIES OF INDIUM-LABELED LEUKOCYTES

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。这种研究具有广泛的应用。这些放射性标记白细胞运输研究最常见的用途是在其他非侵入性研究不能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8年中，在入组各种方案的临床中心患者中进行了23项脓肿定位研究。在这23例患者中，有3例为阳性并接受了适当的治疗：1例血友病合并HIV感染患者的盐性骨髓炎，1例再生障碍性贫血患者的葡萄球菌肺炎，1例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23项铟标记的同种异体白细胞研究中，有3项在慢性肉芽肿病患者中进行，1项用于记录肺部感染的清除情况，第2项用于确认同种异体免疫受体缺乏运输，第3项用于定位发热原因。在所有3例病例中，伽马成像结果用于指导治疗，特别是在不再需要或无效时终止粒细胞输注过程，或防止剖腹探查术。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的自体克隆T细胞的研究在14名患者中没有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用作评价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.