Technetium-99m-labeled long chain fatty acid analogues metabolized by beta-oxidation in the heart.
The development of 99mTc-labeled fatty acid analogues metabolized by beta-oxidation in the myocardium constitutes an unsolved challenge. On the basis of our recent findings that [188Re]tricarbonyl(cyclopentadienylcarbonate)rhenium ([188Re]CpTR-COOH) was recognized as an aromatic compound and was metabolized as such in the body, [99mTc]cyclopentadienyltricarbonyltechnetium ([99mTc]CpTT) was conjugated at the omega-position of pentadecanoic acid to prepare [99mTc]CpTT-PA. When injected into rats, [99mTc]CpTT-PA exhibited the maximum myocardial accumulation and heart-to-blood ratio of 3.85 %ID/g at 1 min and 4.60 at 10 min postinjection, respectively. The metabolic study using isolated Langendorff perfused rat hearts demonstrated that approximately 67% of perfused [99mTc]CpTT-PA was incorporated and [99mTc]CpTT-propionic acid, the metabolite after six cycles of beta-oxidation of [99mTc]CpTT-PA, was detected as the major radiometabolite in the perfusate and myocardium. These findings indicate that [99mTc]CpTT-PA was recognized, transported, and metabolized as a long chain fatty acid analogue for energy production in the myocardium.
Uehara
Tomoya
T
Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
Uemura
Tomoe
T
Hirabayashi
Seiji
S
Adachi
Sayaka
S
Odaka
Kenichi
K
Akizawa
Hiromichi
H
Magata
Yasuhiro
Y
Irie
Toshiaki
T
Arano
Yasushi
Y
D000818:Animals; D001692:Biological Transport; D004734:Energy Metabolism; D005227:Fatty Acids / Q000737:chemistry*; D066298:In Vitro Techniques; D007462:Iodobenzenes / Q000493:pharmacokinetics; D009206:Myocardium / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D010084:Oxidation-Reduction; D051381:Rats; D013667:Technetium; D014018:Tissue Distribution
D005227:Fatty Acids; D007462:Iodobenzenes; D015609:Organotechnetium Compounds; D013667:Technetium; C025391:omega-(4-iodophenyl)pentadecanoic acid; C117025:pentadecanoic acid