KINETIC STUDIES OF INDIUM LABELED LEUKOCYTES

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The kinetic patterns of fresh, frozen-thawed, or cultured human leukocytes are studied by tagging the cells ex vivo with 111 - Indium, a radio- isotopic label, and measuring their distribution throughout the body by means of gamma camera imaging and gamma counting of blood samples. This type of study has widespread applications. The most common use of these radio-labeled 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 muCi of 11 l-Indium per kg of patient weight. Fourteen studies for the purpose of abscess localization were performed in Clinical Center patients enrolled in a variety of protocols in the past 6 years. Two of these 14 were positive and led to appropriate therapy for a case of Salmonella osteomyelitis in a hemophiliac patient with HIV infection, and resection of a diverticular abscess in a patient with Zollinger-Ellison syndrome. In many of the negative studies, unnecessary surgical exploration was avoided. Indium-labeled leukocyte trafficking studies have also been investigated as diagnostic tools is-detecting large vessel inflammation in patients with Takayasu's arteritis. A prospective study performed in collaboration with NIAID and NMD/CC showed that radio-labeled autologous mononuclear cell trafficking could not accurately predict whether symptomatic patients with fever and high sedimentation rates had active arteritis, and thus could not be used to determine whether intervention with anti-inflammatory agents should be initiated. Collaborative trials with the Surgery Branch, NCI, have investigated the diagnostic utility and prognostic application of radio-labeled 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 in response to infusions of TIL cells and cyclophosphamide. Most recently, radio-labeled allogeneic granulocyte trafficking studies have been used to determine whether pulmonary infiltrates in patients with chronic granulomatous disease of childhood (COD) are due to infection or to lung scarring and granuloma formation. Trafficking studies in COD patients with HLA-alloimmunization have been used to predict whether allogeneic cells will survive following transfusion and thus whether a therapeutic trial of granulocyte transfusions is warranted.