Disposition of 125I-labeled recombinant human tumor necrosis factor in the tumor-bearing mouse.
Disposition of [125I]rHu-TNF was elucidated in BALB/c mice bearing Meth A fibrosarcoma 7 days after transplantation. After i.v. administration, [125I]rHu-TNF measured by radioactivity and immunoreactivity biphasically decreased in plasma. Tumor level of [125I]rHu-TNF was the maximum at 1 h, then decreased and finally remained essentially constant. After i.t. administration, plasma level reached the maximum at 1 h. Tumor level decreased quickly and then became essentially constant. [125I]rHu-TNF was suggested to be degraded to small fragments in the tumor. Significant distribution of [125I]rHu-TNF was found in the kidney, lung, liver and tumor. Most tissue levels decreased with time in parallel with plasma levels. [125I]rHu-TNF radioactivity was found in proximal convoluted tubules of kidney and in those areas of tumor consisting of degenerating cells with pyknotic nuclei. Urine contained most of administered radioactivity, which being neither immunoreactive nor protein-bound.
Miyazaki
H
H
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Fujii
T
T
Amejima
H
H
Mikuriya
N
N
Nambu
K
K
Kagemoto
A
A
Nakao
M
M
Oh-e
Y
Y
Matsumoto
K
K
Matsui
Y
Y
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism*; D006207:Half-Life; D007124:Immunoenzyme Techniques; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000493:pharmacokinetics*
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha