Effects of Dextranation on the Pharmacokinetics of Short Peptides. A PET Study on mEGF

详细信息    查看全文

• 作者：Qinghai Zhao ; Vladimir Tolmachev ; Jö ; rgen Carlsson ; Hans Lundqvist ; Johanna Sundin ; Jan-Christer Janson ; and Anders Sundin
• 刊名：Bioconjugate Chemistry
• 出版年：1999
• 出版时间：November 1999
• 年：1999
• 卷：10
• 期：6
• 页码：938 - 946
• 全文大小：96K
• 年卷期：v.10,no.6(November 1999)
• ISSN：1520-4812

文摘

The effects of dextranation on the biodistribution of mouse epidermal growth factor (mEGF, 6 kDa)were assessed. By reductive amination, mEGF was coupled to 13 and 46 kDa dextran. The twodextranated conjugates and free mEGF were labeled with the positron-emitting nuclide ⁷⁶Br (T_1/2 =16 h). After intravenous administration to Sprague Dawley rats, the radioactivity biodistribution wasevaluated by positron emission tomography (PET) and by measurements of dissected tissues. Thedextranation prolonged the retention time in blood, especially when the dextran chain was long. [⁷⁶Br]mEGF-dextran conjugates were shown to have significantly, more than 5 times, lower kidneyaccumulation than the nonconjugated [⁷⁶Br]mEGF. In conclusion, dextranation affects the biodistribution of mEGF in vivo giving a prolonged circulation time, a decreased uptake in kidney, and anincreased spleen accumulation.