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Noninvasive Assessment of Regional Cardiac Adenosine Using Positron Emission Tomography

Zentrum für Physiologie, Heinrich-Heine-Universität Düsseldorf, Düsseldolf, Germany
Institut für Medizin and Institut für Chemie 1, Forschungszentrum Jülich, Jülich, Germany

Correspondence: For reprints contact: Andreas Deussen, Zentrum für Physiologie, Heinrich-Heine-Universitat Düsseldorf, Moorenstr. 5, D-4000 Düsseldorf 1, Germany.

ABSTRACT

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 earner added 1-[¹¹C]-D,L-homocysteine thiolactone (5–27 mCi, 30 mg/kg) was infused over1 min. This intervention, while hemodynamically in effective, increased the plasma homocysteine concentration from 2.5 to 306 µM, which thereafter declined with a T of 28 min to 97 µM 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 radio activity 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 µCi; 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.

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