RT Journal Article
SR Electronic
T1 In Vivo Quantification of Myocardial Dihydropyridine Binding Sites: A PET Study in Dogs
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1227
OP 1233
VO 43
IS 9
A1 Valette, Héric
A1 Dollé, Frédéric
A1 Guenther, Ilonka
A1 Fuseau, Chantal
A1 Coulon, Christine
A1 Hinnen, Françoise
A1 Péglion, Jean-Louis
A1 Crouzel, Christian
YR 2002
UL http://jnm.snmjournals.org/content/43/9/1227.abstract
AB Abnormalities in myocardial L-type Ca2+ channel abundance and function have been described in cardiac hypertrophy and failure. In vivo quantification of the density of these channels using PET and an adequate ligand would provide new insights into cardiac disease. Methods: The dihydropyridine L-type Ca2+ channel antagonist S12968 (3-ethyl 5-methyl (−)-2-[(2-(2-aminoethoxy)ethoxy)methyl]-4-(2,3-dichlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate) was labeled with 11C and injected in various amounts (5–23 nmol), 20 or 30 min apart, into dogs. This protocol allowed a separate evaluation of the density of binding sites (Bmax) as well as association and dissociation rate constants. The parameters were calculated using a nonlinear mathematic model. Results: Using the multiinjection approach, a complete model describing interactions between S12968 and the dihydropyridine binding sites was obtained. Bmax was found to be 19.2 ± 3.3 pmol·mL−1 of tissue. Association and dissociation constants (estimated by Kon/VR and KdVR, respectively) were found to be 0.015 ± 0.01 mL·pmol−1·min−1 and 4.2 ± 2.2 nmol·mL−1, respectively. Conclusion: The present data suggest that it is possible to measure myocardial dihydropyridine binding site density with a single radiosynthesis and a simple PET protocol that is not time consuming (75 min for the total examination, including transmission and emission scans). This methodology can be useful to investigate human cardiac disease in vivo.