RT Journal Article
SR Electronic
T1 SPECT Quantification of Benzodiazepine Receptor Concentration Using a Dual-Ligand Approach
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 783
OP 792
VO 47
IS 5
A1 Philippe Millet
A1 Christophe Graf
A1 Marcelle Moulin
A1 Vicente Ibáñez
YR 2006
UL http://jnm.snmjournals.org/content/47/5/783.abstract
AB The distribution of benzodiazepine receptors in the human brain has been widely studied with SPECT using 123I-iomazenil and semiquantitative approaches, but these methods do not allow quantification of the total receptor site concentration available for binding (B′max) and of the apparent equilibrium dissociation constant (Kd/VR). One of the major obstacles to full quantitative studies is that pharmacologic effects preclude the administration to humans of the high doses of iomazenil required to displace the labeled ligand from the receptors. In this study, we applied a dual-ligand protocol using the unlabeled ligand flumazenil, which lacks pharmacologic effects, to quantify all binding parameters of the benzodiazepine receptor–123I-iomazenil interactions. Methods: 123I-Iomazenil SPECT and MRI were acquired in 8 healthy volunteers, one of whom had participated in a 11C-flumazenil PET experiment. The experimental protocol consisted of injections of 123I-iomazenil and/or unlabeled flumazenil. We developed a kinetic model to integrate the different pharmacokinetics of these 2 ligands. To simplify the model, we assumed linear relationships between iomazenil and flumazenil parameters and adjusted them using a coupled fitting procedure. The resulting constrained 5-parameter model was then used to quantify the biologic parameters. Results: Across regions, we obtained B′max values ranging from 7 to 69 pmol/mL and KdVR values for IMZ from 2.3 to 3.7 pmol/mL. There was a close correlation in the B′max values calculated in the same volunteer using 123I-iomazenil SPECT and 11C-flumazenil PET. Conclusion: The dual-ligand approach can be used to quantify all model parameters with acceptable SEs. This work demonstrates a theoretic framework and initial application of SPECT to quantify binding parameters.