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Myocardial Kinetics of the 11C-Labeled Enantiomers of the Ca2+ Channel Inhibitor S11568: An In Vivo Study

Héric Valette, Frédéric Dollé, Ilonka Guenther, Françoise Hinnen, Chantal Fuseau, Christine Coulon, Jean-Louis Péglion and Christian Crouzel

Service Hospitalier Frédéric Joliot, Direction of Life Sciences, Department of Medical Research, French Atomic Agency, Orsay; and Institut de Recherche Servier, Suresnes, France



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  		FIGURE 1. Time course of myocardial and plasma radioactivity (uncorrected for metabolites) in dog after injection of tracer dose (5.2 nmol) of [11C]S12968.

 


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  		FIGURE 2. Comparison of time course of myocardial radioactivity in dog heart after injection of 2 doses of [11C]S12968. With lower injected dose (5.2 nmol [{blacklozenge}]), time–activity curve remained at plateau with slight downslope. With higher injected dose (13.3 nmol [{blacksquare}]), higher uptake followed by more rapid washout of radioactivity was observed.

 


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  		FIGURE 3. Images of dog heart after injection of 5 nmol [11C]S12967 or [11C]S12968, 5 and 15 min after injection.

 


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  		FIGURE 4. Metabolic profile of S12968 in dogs (n = 4). Average of 70% of unchanged tracer was found in plasma 20 min after injection.

 


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  		FIGURE 5. Comparison of chemical structures of S12968 and (±)-amlodipine. In spite of similarity of chemical structures, in vivo behaviors of the 2 compounds are extremely different (8).

 




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