TY - JOUR A1 - Mirtschink, P. A1 - Stehr, S.N. A1 - Pietzsch, H.J. A1 - Bergmann, R. A1 - Pietzsch, J. A1 - Wunderlich, G. A1 - Heintz, A.C. A1 - Kropp, J. A1 - Spies, H. A1 - Kraus, Werner A1 - Deussen, A. A1 - Walther, M. T1 - Modified "4+1" Mixed Ligand Technetium-Labeled Fatty Acids for Myocardial Imaging: Evaluation of Myocardial Uptake and Biodistribution JF - Bioconjugate chemistry N2 - Our group previously synthesized 99mTc-labeled fatty acids suitable for myocardial metabolism and flow imaging. In this set of experiments, 29 new analogues were synthesized according to the “4 + 1” mixed ligand approach with some specific differences. Conventional “4 + 1” 99mTc-fatty acids are built in the sequence: Tc-chelate, alkyl chain, and carboxylic group. We developed compounds following a new design with the sequence: carboxylic group, alkyl chain, Tc-chelate, and lipophilic tail. Therefore, the 99mTc-chelate was transferred to a more central position of the compound, aiming toward an improved myocardial profile and an accelerated liver clearance. In this context, several functional groups incorporated in the lipophilic tail section were tested to evaluate their influence on the compound's character. In addition to biodistribution studies in vivo, the myocardial first-pass extraction of the compounds was tested in an isolated Langendorff rat heart model. A satisfactory myocardial uptake of up to 20% of the injected dose (% ID) in the perfused heart and a fast liver clearance in vivo with only 0.29% ID/g at 60 min postinjection demonstrate that the induced molecular modifications affect the kinetics of 99mTc-radiolabeled fatty acid compounds favorably. From the data set, rules for estimating the biodistribution of fatty acids tracers are deduced. PY - 2008 DO - https://doi.org/10.1021/bc700164c SN - 1043-1802 SN - 1520-4812 VL - 19 IS - 1 SP - 97 EP - 108 CY - Washington, DC AN - OPUS4-16499 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -