In vivo quantification and parametric images of the cardiac beta-adrenergic receptor density.
Previous studies showed that the in vivo concentration of beta-adrenergic receptor sites can be estimated by PET using (-)-4-((S)-3-tert-butylamino-2-hydroxypropoxy)-1,3-dihydrobenzoimidazol-2-one (CGP 12177), a hydrophilic ligand. A graphic method was previously proposed and used by several groups. However, this approach was not completely validated. The purpose of this study was to improve and confirm the validity of this approach through a better knowledge of the associated ligand-receptor model, estimated for the first time using the multiinjection approach.


METHODS
The concentration of beta-adrenergic receptor sites was estimated for mini pigs using 2 methods. The first was the usual multiinjection approach, which permits estimation of all model parameters, including receptor concentration. However, this approach needs a complex protocol, including blood sampling, thereby making it difficult to use for studies on patients. The second method was the CGP 12177 graphic method. This approach permits the estimation of only receptor concentration but has the advantage of not requiring blood sampling. Another advantage is the ability to generate parametric images easily.


RESULTS
Using the multiinjection approach, we obtained for the first time a complete model describing interactions between CGP 12177 and beta-adrenergic receptors. Knowledge of all parameters of this model permitted good validation of the assumptions included in the graphic method. The concentration of beta-adrenergic receptor sites in mini pigs was estimated at 15.2 +/- 3.4 pmol/mL.


CONCLUSIONS
The graphic method has been improved by taking into account various phenomena, such as protein binding and the nonlinearity between plasma concentration and injected dose. This method is now usable for patient studies and offers the ability to estimate the beta-adrenergic receptor concentration from a single PET experiment without blood sampling. Parametric imaging will enable screening of the receptor site location and observation of potential anomalies in patients.
Delforge
Jacques
J
Service Hospitalier Frédéric Joliot, Commissariat à l'Energie Atomique/Direction des Sciences du Vivant, Orsay, France. jacques.delforge@cea.fr
Mesangeau
Didier
D
Dolle
Frédéric
F
Merlet
Pascal
P
Loc'h
Christian
C
Bottlaender
Michel
M
Trebossen
Régine
R
Syrota
André
A
D018663:Adrenergic Agents; D000818:Animals; D002250:Carbon Radioisotopes; D006321:Heart / Q000000981:diagnostic imaging; D008297:Male; D008962:Models, Theoretical; D009206:Myocardium / Q000378:metabolism*; D011412:Propanolamines; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000032:analysis*; D013552:Swine; D013556:Swine, Miniature; D014055:Tomography, Emission-Computed
D018663:Adrenergic Agents; D002250:Carbon Radioisotopes; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C033394:CGP 12177