Pharmacokinetics, tissue distribution, and cell localization of ( sup 35 S)methionine-labeled recombinant human and murine alpha interferons in mice

Journal Article · Wed Aug 01 00:00:00 EDT 1990 · Cancer Research; (USA)

OSTI ID:6649739

Johns, T G; Kerry, J A; Veitch, B A; Mackay, I R; Tutton, P J; Tymms, M J; Cheetham, B F; Hertzog, P J; Linnane, A W ^[1]

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1. Monash Univ., Clayton, Victoria (Australia)

The pharmacokinetics, tissue distribution, cell localization, and penetration into tumor xenografts of recombinant (35S)methionine-labeled human alpha interferon (HuIFN-alpha) and murine alpha interferon (MuIFN-alpha) were examined in mice. Both interferons (IFNs) were removed from the blood in a rapid biphasic manner; HuIFN-alpha was cleared faster than MuIFN-alpha. Tissues were analyzed for radioactivity and over 90% of the IFNs was accounted for. The IFNs were detected predominantly in liver, kidney, gastrointestinal tract, pancreas, spleen, and lung. The levels of MuIFN-alpha compared with HuIFN-alpha were greater in the liver, spleen, and lung and less in the kidney, pancreas, and gastrointestinal tract. Heart, brain, testes, thymus, lymph nodes, fat, skin, and skeletal muscle contained much lower but measurable levels of both IFNs. There was penetration of HuIFN-alpha into tumor xenografts. The pharmacokinetics of IFN-alpha were independent of the strain of mouse, BALB/c or CBA, immune deprivation, or the presence of a tumor xenograft. Autoradiography of tissue sections from mice given injections of HuIFN-alpha or MuIFN-alpha indicated focal radioactivity in proximal convoluted tubules in the kidney and diffuse radioactivity in the liver, gastrointestinal tract, and pancrease. MuIFN-alpha, but not HuIFN-alpha, showed intense localization in cells in hepatic sinusoids, marginal zones in the spleen, and pulmonary alveolar walls, suggesting uptake by cells of the monocyte/macrophage lineage in these sites. The study shows the utility of biosynthetic labeling for pharmacokinetic studies of cytokines, clear differences in tissue distribution of IFN-alpha according to its species of origin, and targeting of homologous IFN-alpha to cells of the monocytic lineage.

• OSTI ID: 6649739
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50:15; ISSN 0008-5472; ISSN CNREA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
550600 -- Medicine
59 BASIC BIOLOGICAL SCIENCES
62 RADIOLOGY AND NUCLEAR MEDICINE
AMINO ACIDS
ANIMALS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL LOCALIZATION
CARBOXYLIC ACIDS
CHEMOTHERAPY
DAYS LIVING RADIOISOTOPES
DISEASES
DISTRIBUTION
DRUGS
EVEN-ODD NUCLEI
EXPERIMENTAL NEOPLASMS
GROWTH FACTORS
INTERFERON
ISOTOPES
KINETICS
LIGHT NUCLEI
LIPOTROPIC FACTORS
LYMPHOKINES
MAMMALS
MELANOMAS
METHIONINE
MICE
MITOGENS
NEOPLASMS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SULFUR 35
SULFUR ISOTOPES
THERAPY
TISSUE DISTRIBUTION
VERTEBRATES