Synthesis and biological evaluation of a new type of 99mtechnetium-labeled Fatty Acid for myocardial metabolism imaging.
Technetium-labeled fatty acids intended for myocardial metabolism imaging and the respective rhenium model complexes were synthesized according to the "4 + 1" mixed-ligand approach and investigated in vitro and in vivo. The non-radioactive rhenium model complexes were characterized by NMR, IR, and EA, and the geometrical impact of the chelate unit on the integrity of the fatty acid head structure was determined by single-crystal X-ray analyses. To estimate the diagnostic value of the 99mTc-labeled fatty acids, the compounds were investigated in experiments in vitro and in biodistribution studies using male Wistar rats. The new fatty acid tracers contain the metal core in the oxidation states +3, well-wrapped in a trigonal-bipyramidal coordination moiety, which is attached at the omega-position of a fatty acid chain. This structural feature is considered to be a good imitation of the well-established iodinated phenyl fatty acids. High heart extraction in perfused heart studies (up to 26% injected dose (ID)) and noticeable heart uptake of the 99mTc tracers in vivo being in the order of 2% ID/g at 5 min (postinjection, pi.), accompanied by a good heart to blood ratio of 8, confirms that the new Tc compounds are suitable as fatty acid tracers.
Walther
Martin
M
Institute of Radiopharmacy, Research Center Dresden-Rossendorf, PF 510119, D-01314 Dresden, Germany. m.walther@fzd.de
Jung
Christian M
CM
Bergmann
Ralf
R
Pietzsch
Jens
J
Rode
Katrin
K
Fahmy
Karim
K
Mirtschink
Peter
P
Stehr
Sebastian
S
Heintz
Anke
A
Wunderlich
Gerd
G
Kraus
Werner
W
Pietzsch
Hans-Juergen
HJ
Kropp
Joachim
J
Deussen
Andreas
A
Spies
Hartmut
H
D000818:Animals; D003300:Copper / Q000737:chemistry; D018360:Crystallography, X-Ray; D005227:Fatty Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics; D006321:Heart / Q000187:drug effects; D008024:Ligands; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D013667:Technetium / Q000737:chemistry*
D005227:Fatty Acids; D008024:Ligands; D013667:Technetium; D003300:Copper