Interferon-induced changes in pharmacokinetics and tumor uptake of 111In-labeled antimelanoma antibody 96. 5 in melanoma patients
The type I interferons (both partially purified human leukocyte interferon (HuIFN-alpha) 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-alpha could increase tumor acquisition of the antimelanoma antibody 96.5 in vivo, five patients with metastatic malignant melanoma were treated with HuIFN-alpha at a dose of 3 X 10(6) units daily by im administration. Twenty-four hours after the first dose of HuIFN-alpha, 1 mg of antibody 96.5 labeled with 5 mCi of /sup 111/In was coadministered with 19 mg of unlabeled 96.5. Five patients matched for metastatic site and lesion size who had not received HuIFN-alpha 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-alpha, there was a statistically significant increase in the plasma half-life of the /sup 111/In 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-alpha 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-alpha-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.
- Research Organization:
- Univ. of Texas System Cancer Center, Houston (USA)
- OSTI ID:
- 5290061
- Journal Information:
- J. Natl. Cancer Inst.; (United States), Journal Name: J. Natl. Cancer Inst.; (United States) Vol. 80:3; ISSN JNCIA
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BIOLOGICAL HALF-LIFE
BLOOD-PLASMA CLEARANCE
CLEARANCE
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
IMMUNOLOGY
INDIUM 111
INDIUM ISOTOPES
INTERFERON
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
KINETICS
LYMPHOKINES
MEDICINE
MELANOMAS
MINUTES LIVING RADIOISOTOPES
MITOGENS
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
PATIENTS
PROTEINS
RADIOIMMUNOLOGY
RADIOIMMUNOTHERAPY
RADIOISOTOPES
RADIOLOGY
RADIOTHERAPY
REACTION KINETICS
THERAPY
TISSUE DISTRIBUTION
UPTAKE