Structure–biodistribution relation of neutral 99mTc(CO) 3-complexes with tridentate N-substituted derivatives of aminoethylglycine and phenylenediamine

Abstract

Derivatives of ethylenediamine- N-acetic acid (EDAA = N-aminoethylglycine = AEG) and ortho-phenylenediamine- N-acetic acid (PDAA) with uncharged substituents on one or both of the amines form neutral complexes with a [ 99mTc(CO) 3] +-moiety. We studied the influence of different modifications at the amines (e.g., with methyl, ethyl, butyl or benzyl groups) on the behaviour of the 99mTc(CO) 3-complexes in vivo in mice, with special focus on blood–brain barrier (BBB) passage. The complexes have been characterised by reversed phase HPLC, log P, electrophoresis and some of them also by LC–MS. Log P values of the 99mTc–tricarbonyl complexes varied from −0.52 (AEG) to 2.5 ( N, N′-dibenzyl-EDAA). With increasing lipophilicity, more of the activity was found in liver and intestines as compared to kidneys and urine for the more polar complexes. Brain uptake was found for the 99mTc(CO) 3-complexes with N, N′-dibutyl-ethylenediamine- N-acetic acid (0.34% of I.D. after 2 min) and ortho-phenylenediamine- N-acetic acid (0.22% of I.D. after 2 min).