Interferon-Induced Changes in Pharmacokinetics and Tumor Uptake of 111In-Labeled Antimelanoma Antibody 96.5 in Melanoma Patients

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Abstract
The type I interferons [both partially purified human leukocyte interferon (HuIFN-α) and recombinant alpha interferon] and the type II interferons have been shown to increase the expression of tumor-associated antigens in vitro. To determine whether HuIFN-α could increase tumor acquisition of the antimelanoma antibody 96.5 in vivo, five patients with metastatic malignant melanoma were treated with HuIFN-α at a dose of 3 × 106 units daily by im administration. Twenty-four hours after the first dose of HuIFN-α, 1 mg of antibody 96.5 labeled with 5 mCi of 111In was coadministered with 19 mg of unlabeled 96.5. Five patients matched for metastatic site and lesion size who had not received HuIFN-α were also given a dose of 5 mCi of radiolabeled 96.5 at the same total antibody dose (20 mg). In patients treated with HuIFN-α, there was a statistically significant increase in the plasma half-life of the 111In label (39.7 ± 3.3 hr) compared to the untreated control group (29.8 ± 3.2 hr). In addition, there was an increase in the apparent volume of distribution of the antibody in the HuIFN-α group (5.56 ± 0.67 L) compared to controls (3.15 ± 0.5 L) suggesting both an increased immediate extravascular distribution of radiolabeled antibody and a decrease in the subsequent rate of clearance of antibody from plasma. These two phenomena result in a 28% decrease in the area under the concentration curve in the HuIFN-α-treated group compared to controls. Computer analysis of whole-body scans from patients showed a threefold increase in radiolabeled antibody distributed to tumor relative to blood pool but no change in organ: blood ratios for liver, spleen, bone, or kidney compared to controls. This pilot study suggests that treatment of patients with HuIFN-α results in an improved distribution of radiolabeled antibody to tumor target without a concomitant increase of label in normal nontarget tissues. In addition, this change in whole-body distribution of antibody is manifested by changes in the pharmacokinetic parameters measured for monoclonal antibody. [J Natl Cancer Inst 1988;80:160–165]

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