Myocardial uptake and biodistribution of newly designed technetium-labelled fatty acid analogues.
OBJECTIVE
In an effort to develop 99mTc-labelled fatty acids (FAs) for myocardial metabolism and flow imaging, several Tc analogues according to the '3+1' and the '4+1' mixed-ligand approach were synthesized and myocardial extraction was evaluated in non-working isolated guinea pig hearts. An example of biodistribution patterns in guinea pigs was determined by using one FA analogue.


METHODS
The coordination moieties contain a +5, respectively +3, oxidation state metal core attached to the end position of a FA chain. FA complexes of the '3+1' and the '4+1' mixed-ligand type were prepared and investigated using the isolated heart model. To estimate the diagnostic value of the analogue 99mTc-FAs, the biodistribution of one well-extracted FA was evaluated.


RESULTS
The '4+1' FA compounds achieved the highest uptake rates of all the technetium FAs investigated. In particular, the '4+1' 99mTc-C11-FA achieved at least a 2-fold higher ventricular extraction of the applied activity than the established control tracers including omega-(p-[123I]iodophenyl)pentadecanoic FAs (BMIPP and IPPA) and Tc-MIBI. Furthermore, the '4+1' dodecanoic FA derivative and the thiadodecanoic FA derivative showed an extraction comparable to established 123I-labelled tracers. Biodistribution experiments performed for the thiadodecanoic FA derivative indicated a good heart/blood and heart/lung ratio and also a high uptake in the liver. In contrast, '3+1' 99mTc complexes showed a low myocardial extraction rate. Nevertheless, the differentiation in the extraction profile, which depends on the FA chain length and structure, indicates a specific heart uptake of these 99mTc-labelled FA derivatives as well.


CONCLUSIONS
The excellent extraction rates found for '4+1' 99mTc-FAs indicate possibly promising structures for innovative myocardial tracers.
Heintz
Anke C
AC
Department of Anesthesiology, Medical Faculty, Technical University Dresden, Dresden, Germany. anke.heintz@mailbox.tu-dresden.de
Jung
Christian M
CM
Stehr
Sebastian N
SN
Mirtschink
Peter
P
Walther
Martin
M
Pietzsch
Jens
J
Bergmann
Ralf
R
Pietzsch
Hans-Jürgen
HJ
Spies
Hartmut
H
Wunderlich
Gerd
G
Kropp
Joachim
J
Deussen
Andreas
A
D000818:Animals; D005227:Fatty Acids / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D013667:Technetium / Q000493:pharmacokinetics*
D005227:Fatty Acids; D019275:Radiopharmaceuticals; D013667:Technetium