In vivo quantification of myocardial dihydropyridine binding sites: a PET study in dogs.
Abnormalities in myocardial L-type Ca(2+) 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 Ca(2+) 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 (11)C 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 (B(max)) 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. B(max) was found to be 19.2 +/- 3.3 pmol x mL(-1) of tissue. Association and dissociation constants (estimated by K(on)/VR and K(d)VR, respectively) were found to be 0.015 +/- 0.01 mL x pmol(-1) x min(-1) and 4.2 +/- 2.2 nmol x mL(-1), respectively.


CONCLUSIONS
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.
Valette
Héric
H
Department of Medical Research, Direction of Life Sciences, Service Hospitalier Frédéric Joliot, French Atomic Agency, Orsay, France. valette@shfj.cea.fr
Dollé
Frédéric
F
Guenther
Ilonka
I
Fuseau
Chantal
C
Coulon
Christine
C
Hinnen
Françoise
F
Péglion
Jean-Louis
JL
Crouzel
Christian
C
D000818:Animals; D001665:Binding Sites; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002250:Carbon Radioisotopes; D004095:Dihydropyridines / Q000378:metabolism; D004285:Dogs; D005260:Female; D006321:Heart / Q000000981:diagnostic imaging; D009206:Myocardium / Q000378:metabolism*; D013997:Time Factors; D014055:Tomography, Emission-Computed
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002250:Carbon Radioisotopes; D004095:Dihydropyridines; C067838:S 11568