Tissue distribution of recombinant human tumor necrosis factor alpha derivative in mice.
OBJECTIVE
To study the tissue distribution and its mechanism of a new recombinant tumor necrosis factor alpha derivative (rhTNF alpha Da) in mice.


METHODS
125I-rhTNF alpha Da was prepared by Iodogen method. Tissue distribution of 125I-rhTNF alpha Da in mice was studied by determining radioactivity of tetrachloroacetic acid (TCA)- precipitable fraction in tissues. The isolated heart-lung perfusion study using 125I-rhTNF alpha Da perfusate was carried out to study the distribution characteristics of 125I-rhTNF alpha Da in lung.


RESULTS
Except for thyroid, AUC of the TCA-precipitable 125I-rhTNF alpha Da in tissues was highest in lung, which was 12.2-fold of that in serum, while concentrations in other tissues were all lower than that in serum. Perfusion study in vitro revealed that the concentration of radio-labeled peptide in lung was higher than that in perfusate. On the contrary, level in heart was much lower than that in perfusate. The overall distribution of 125I-rhTNF alpha Da in lungs showed rapidly equilibratory, dose-dependent, saturable, competitive, and highly affinitive, with Kd 47.6 pmol.L-1 and Bmax 348 fmol.g-1 (lung tissue).


CONCLUSIONS
The specific distribution of rhTNF alpha Da in lungs was its distinctive characteristics.
Chai
B X
BX
Department of Pharmacology, Institute of Radiation Medicine, Beijing, China.
Tang
Z M
ZM
Liu
X W
XW
Tu
M
M
D000818:Animals; D005260:Female; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D011897:Random Allocation; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000493:pharmacokinetics*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha