Original Articles

Tissue distribution of recombinant human tumor necrosis factor alpha derivative in mice

Biao-xin Chai, Zhong-ming Tang, Xiu-wen Liu, Min Tu


To study the tissue distribution and its mechanism of a new recombinant tumor necrosis factor alpha derivative (rhTNF alpha Da) in mice.
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.
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).
The specific distribution of rhTNF alpha Da in lungs was its distinctive characteristics.

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