Noninvasive assessment of regional cardiac adenosine using positron emission tomography.
One of the early metabolic changes associated with myocardial ischemia is the breakdown of adenine nucleotides resulting in the enhanced production of adenosine. In order to image regional cardiac adenosine by positron emission tomography (PET) the enzymatic conversion of adenosine into [11C]-S-adenosylhomocysteine ([11C]SAH) was used in the presence of 11C-labeled homocysteine thiolactone (adenosine + [11C] - homocysteine-->[11C] - SAH + H2O). Following production of an experimental coronary constriction in anesthetized dogs carrier added 1-[11C]-D,L-homocysteine thiolactone (5-27 mCi, 30 mg/kg) was infused over 1 min. This intervention, while hemodynamically ineffective, increased the plasma homocysteine concentration from 2.5 to 306 microM, which thereafter declined with a T1/2 of 28 min to 97 microM after 60 min. During the first minutes following infusion of [11C] homocysteine, the radioactivity concentration in the blood pool, the nonischemic and the ischemic myocardium were similar. Between 20 and 60 min, however, the regional radioactivity concentration was highest in the perfusion area of the stenosed vessel: 6.6% compared to 5.2 and 5.2% of the injected dose per 1 I tissue. The elevated radioactivity concentration was strictly confined to the perfusion area of the occluded artery. Using [35S]-L-homocysteine (20 microCi; 30 mg/kg) chromatographic separation of SAH in tissue extracts confirmed that the radioactivity accumulation was due to trapping of adenosine in the cellular SAH-pool. These experiments provide first evidence that 1-[11C]homocysteine thiolactone can be successfully used to assess regional adenosine formation in the heart with PET via measurement of [11C] SAH accumulation.
Deussen
A
A
Zentrum für Physiologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Henrich
M
M
Hamacher
K
K
Borst
M M
MM
Herzog
H
H
Coenen
H H
HH
Stöcklin
G
G
Feinendegen
L E
LE
Schrader
J
J
D000241:Adenosine / Q000096:biosynthesis / Q000493:pharmacokinetics*; D000818:Animals; D002250:Carbon Radioisotopes; D004285:Dogs; D004734:Energy Metabolism; D006710:Homocysteine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D006710:Homocysteine; C007957:homocysteine thiolactone; D000241:Adenosine