In Vivo Quantification of Myocardial Dihydropyridine Binding Sites: A PET Study in Dogs

Journal of Nuclear Medicine

Héric Valette¹  Christine Coulon¹  Françoise Hinnen¹  Chantal Fuseau¹  Jean-Louis Péglion¹  Ilonka Guenther¹  Frédéric Dollé¹  Christian Crouzel¹ 

关键词: PET;    heart;    dihydropyridine binding;    ¹¹C-S12968;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown