Lipophilic derivatives of 99mTc(Sn)pyridoxylidenephenylalanine: a structure distribution relationship (SDR) study on...

The chemical and biological properties of several lipophilic derivatives of 99mTc(Sn)pyridoxylidenephenylalanine were investigated, and some clearcut structure distribution relationships (SDRs) were derived from the results: (i) An increase in total lipophilicity of the complex molecule decreases its urinary excretion after intravenous administration. (ii) A lipophilic substituent in the para position of the benzene ring of the phenylalanine moiety decreases the urinary excretion of the complex, but it delays the hepatobiliary transit. (iii) A lipophilic substituent in the ortho position accelerates the hepatobiliary transit along with the depression of the urinary excretion. (iv) When both para and ortho positions are occupied by lipophilic substituents, the ortho-effect (acceleration) is predominant over the para-effect (inhibition) on the hepatobiliary transit. These SDRs are discussed in terms of the chemical structure of the complex molecules, and guide-lines for designing new 99mTc-labeled hepatobiliary agents are proposed.