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.
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Johannsen, B., Berger, R., Brust, P. et al. Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake. Eur J Nucl Med 24, 316–319 (1997). https://doi.org/10.1007/BF01728770
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DOI: https://doi.org/10.1007/BF01728770