Binding properties of the cerebral α4β2 nicotinic acetylcholine receptor ligand 2-[18F]fluoro-A-85380 to plasma proteins

Introduction: To determine the availability of nicotinic acetylcholine receptors in different human brain regions using the positron emission tomography (PET) radioligand 2-[F-18]fluoro-A-85380 (2-[F-18]FA) and invasive approaches for quantification, it is important to correct the arterial input function as well for plasma protein binding (PPB) of the radioligand as for radiolabeled metabolites accumulating in blood. This study deals with some aspects of PPB of 2-[F-18]FA. Methods: Patients with different neurological disorders (n = 72), such as Parkinson's disease, Alzheimer's disease and multiple sclerosis, and a group of healthy volunteers (n = 15) subjected for PET imaging were analyzed for their PPB level of 2-[F-18]FA using ultrafiltration. Protein gel electrophoresis of plasma samples was performed to identify the binding protein of 2-[F-18]FA. The dependency of PPB on time and on free ligand concentration was analyzed to obtain the binding parameters B-max, and K-d. Results: Albumin was identified to be the binding protein of 2-[F-18]FA. PPB of 2-[F-18]FA was low at 17 +/- 4% and did not show significant differences between the groups of patients. Corresponding to this, a narrow range of plasma albumin of 0.62 +/- 0.05 mM was observed. B,m was determined as twice the albumin concentration, which indicates two binding sites for 2-[F-18]FA on the protein. No time dependence of the PPB could be observed. By relating PPB to B-max, an average Kd value of 6.0 +/- 1.5 mM was obtained. Conclusion: This study shows the dependency of PPB of 2-[F-18]FA on human albumin plasma concentration. An equation utilizing B-max and K-d to easily estimate PPB is presented. (c) 2006 Elsevier Inc. All rights reserved.