J Nucl Med. 2008; 49 (Supplement 1):302P
Radiopharmaceutical Chemistry: New Chemistry-OtherNew Chemistry-Other Posters |
Synthesis of F-18 labeled 6-thia fatty acid analog and its evaluation in mouse heart
D. Kim1,
Y. Choe1,
J. Choi1,
Y. Choi1,
K. Lee1 and
B. Kim1
1 Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
1285
Objectives: Fatty acids are substrates for energy metabolism in myocardium. Therefore, radiolabeled fatty acid analogs are useful for evaluation of fatty acid utilization in myocardium. In the present study, 17-[4-(2-[F-18]fluoroethyl)-1H-1,2,3-triazol-1-yl]-6-thia-heptadecanoic acid ([F-18]1) was synthesized and its utility was evaluated in mouse heart.
Methods: [F-18]1 was synthesized from 4-[F-18]fluoro-1-butyne and 17-azido 6-thia fatty acid analog using a click labeling method. ICR mice injected with [F-18]1 were sacrificed at 1, 5, 10, 30, and 60 min p.i., and the tissues were counted. In another set of experiment, ICR mice were injected i.p. with etomoxir (40 mg/kg) at 2 h prior to the injection with [F-18]1 and sacrificed at 10 and 30 min after injection of the radiotracer. In metabolite analysis experiment, the heart samples were collected at 10 and 30 min p.i., homogenized in a mixture of CHCl3-CH3OH-NaOH, and centrifuged. The resulting organic layer, aqueous layer, and the pellet were respectively counted and analyzed.
Results: Tissue distribution of [F-18]1 in mice showed high radioactivity accumulation in the heart (3.70 %ID/g at 1 min, 3.28 %ID/g at 10 min, and 3.01 %ID/g at 60 min). The maximal heart to blood uptake ratio was 6.5 at 5 min, and myocardial elimination half-life was longer than 60 min. Pretreatment of etomoxir, a CPT I inhibitor, reduced the myocardial uptake at 30 min by 53%. In metabolite analysis, most radioactivity was detected in the pellet (74%) when the heart samples were homogenized. These results, along with precipitation upon TCA treatment of the pellet suggest metabolic trapping of [F-18]1 in myocardium.
Conclusions: [F-18]1 may hold promise as a PET radiotracer for evaluation of fatty acid utilization in myocardium.
