PT  - JOURNAL ARTICLE
AU  - Uehara, Tomoya
AU  - Hirabayashi, Seiji
AU  - Uemura, Tomoe
AU  - Odaka, Kenichi
AU  - Magata, Yasuhiro
AU  - Akizawa, Hiromichi
AU  - Irie, Toshiaki
AU  - Arano, Yasushi
TI  - A Tc-99m-labeled long chain fatty acid analog metabolized by the heart
DP  - 2006 May 01
TA  - Journal of Nuclear Medicine
PG  - 518P--518P
VI  - 47
IP  - suppl 1
4099  - http://jnm.snmjournals.org/content/47/suppl_1/518P.3.short
4100  - http://jnm.snmjournals.org/content/47/suppl_1/518P.3.full
SO  - J Nucl Med2006 May 01; 47
AB  - 1888 Objectives: Development of 99mTc-labeled long chain fatty acid analogues metabolized by beta-oxidation in myocardium still constitutes an unsettled challenge. A recent study showed that [188Re]tricarbonyl (carboxycyclopentadienyl) rhenium was recognized as an aromatic compound and metabolized as such by the body. Based on these findings, cyclopentadienyltricarbonyltechnetium (CpTT) was conjugated to the ω-position of pentadecanoic acid to prepare CpTT-PA. Biodistribution and myocardial metabolism of CpTT-PA were investigated in rats to estimate the chemical design for developing 99mTc-labeled fatty acid analog. Methods: The ferrocene precursor, 15-ferrocenoyl- tetradecanoic acid methyl ester was prepared by Friedel-Crafts reaction using ferrocene and 1-methyl pentadecanoic acid chloride in the presence of AlCl3. CpTT-PA was prepared by the double ligand transfer reaction of the ferrocene precursor with 99mTcO4-, followed by the reduction of acyl-CpTT to alkyl-CpTT and subsequent hydrolysis of the methyl ester. The chemical structure of CpTT-PA was confirmed by HPLC using well-characterized rhenium compound as a reference. Biodistribution studies were performed after intravenous injection of CpTT-PA to rats. SPECT images were also taken after injection of CpTT-PA to rats. Myocardial metabolism of CpTT-PA was assessed using the isolated Langendorff-perfusded rat heart model. Results: CpTT-PA was obtained with radiochemical yield and purity of 10.1 % and over 93 %, respectively. When injected to rats, CpTT-PA exhibited the highest myocardial accumulation of 3.85 %ID/g at 1 min postinjection, followed by a gradual decrease with times. Due to the faster clearance of radioactivity from the blood, CpTT-PA registered the heart- to-blood ratios of radioactivity of 2.93, 4.60 and 3.44 at 5, 10 and 30 min postinjection. Myocardial accumulation of CpTT-PA was also confirmed by SPECT studies. The metabolic study using isolated Langendorff-perfused rat hearts demonstrated that the major radiometabolite in the perfusate and in the myocardium had a retention time identical to that of 4-cyclopentadienyltricarbonyltechnetium butyric acid, the metabolite after six cycles of beta-oxidation of CpTT-PA. Conclusions: CpTT-PA exhibited significant myocardial accumulation and heart-to-blood ratios of radioactivity, which visualized rat myocardium by SPECT. CpTT-PA was also recognized as a substrate for beta-oxidation by the myocardium. These findings indicated that CpTT-PA would constitute a potential candidate for SPECT-based myocardial metabolic studies.