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

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 [Tc-99m(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 Tc-99m(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. LogP values of the Tc-99m-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 Tc-99m(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). (c) 2006 Elsevier Ltd. All rights reserved.status: publishe