Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake |
| |
Authors: | Bernd Johannsen Ralf Berger Peter Brust Hans-Juergen Pietzsch Matthias Scheunemann Sepp Seifert Hartmut Spies Rosemarie Syhre |
| |
Institution: | (1) Institut für Bioanorganische und Radiopharmazeutische Chemie, Forschungszentrum Rossendorf e.V., PF 510 119, D-01314 Dresden, Germany |
| |
Abstract: | Low brain uptake is a generally accepted problem in developing technetium-99m brain receptor imaging agents. For a class of potential 5-HT2A receptorbinding agents we tried to improve the original low brain uptake of 0.4% injected dose (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules. Because of the presence of a protonable nitrogen, which according to the pK
a value leads to ionization of the molecule at blood pH, the pK
a value was considered to be the parameter most suitable for adjustment of lipophilicity. Insertion of ether-oxygen in the molecule of five candidates lowers the apparent pK
a value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID at 5 min. The direct relationship between brain uptake and apparent pK
a cannot be simply explained by the increase in the pK
a-governed proportion of the neutral species. |
| |
Keywords: | Blood-brain barrier Brain uptake Serotonin receptor binding technetium-99m complexes pK
a values Lipophilicity |
本文献已被 SpringerLink 等数据库收录! |