Binding properties of the cerebral alpha4beta2 nicotinic acetylcholine receptor ligand 2-[18F]fluoro-A-85380 to plasma proteins.
BACKGROUND
To determine the availability of nicotinic acetylcholine receptors in different human brain regions using the positron emission tomography (PET) radioligand 2-[18F]fluoro-A-85380 (2-[18F]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-[18F]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-[18F]FA using ultrafiltration. Protein gel electrophoresis of plasma samples was performed to identify the binding protein of 2-[18F]FA. The dependency of PPB on time and on free ligand concentration was analyzed to obtain the binding parameters Bmax and Kd.


RESULTS
Albumin was identified to be the binding protein of 2-[18F]FA. PPB of 2-[18F]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. Bmax was determined as twice the albumin concentration, which indicates two binding sites for 2-[18F]FA on the protein. No time dependence of the PPB could be observed. By relating PPB to Bmax, an average Kd value of 6.0+/-1.5 mM was obtained.


CONCLUSIONS
This study shows the dependency of PPB of 2-[18F]FA on human albumin plasma concentration. An equation utilizing Bmax and Kd to easily estimate PPB is presented.
Sorger
Dietlind
D
Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany. sord@medizin.uni-leipzig.de
Becker
Georg Alexander
GA
Hauber
Katharina
K
Schildan
Andreas
A
Patt
Marianne
M
Birkenmeier
Gerd
G
Otto
Andreas
A
Meyer
Philipp
P
Kluge
Magnus
M
Schliebs
Reinhard
R
Sabri
Osama
O
D001384:Azetidines / Q000493:pharmacokinetics*; D001798:Blood Proteins / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000097:blood* / Q000000981:diagnostic imaging; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism*
C119803:2-fluoro-3-(2-azetidinylmethoxy)pyridine; D001384:Azetidines; D001798:Blood Proteins; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2