Figure 22.

Peptide metabolism and artifacts of brain uptake of radiolabeled peptide. (A) Rapid a of trichloroacetic acid (TCA)-precipitable plasma radioactivity following the IV injection of [¹²⁵I]-EGF in the rat. (B) Brain uptake of radioactivity is increased >10-fold following the IV injection of [¹²⁵I]-EGF as compared to brain uptake after the IV injection of [¹¹¹In]-EGF. (A,B) drawn from data reported in [805]. (C) The brain/plasma ratio of radioactivity is equal to the brain volume of distribution (VD), and this is plotted against the plasma AUC for 3 forms of radio-iodinated BDNF: [¹²⁵I]-BDNF, [¹²⁵I]-PEG²⁰⁰⁰-BDNF, and [¹²⁵I]-PEG⁵⁰⁰⁰-BDNF. The progressive pegylation of BDNF with PEG²⁰⁰⁰ and then PEG⁵⁰⁰⁰ blocks the peripheral metabolism of BDNF, as reflected in the increasing plasma AUC. As the BDNF metabolism is progressively inhibited, the brain VD of BDNF decreases. The Vo, 13 ± 1 μL/g, shown by the horizontal bar is the brain plasma volume measured with [¹⁴C]-rat albumin. The brain VD of BDNF following pegylation with PEG⁵⁰⁰⁰ completely suppresses peripheral metabolism of the BDNF and the brain VD = Vo, which shows that BDNF does not cross the BBB. Reproduced with permission from [1139], Copyright© 1997 Springer-Nature.