Gender dependent rate of metabolism of the opioid receptor-PET ligand [18F]fluoroethyldiprenorphine.
OBJECTIVE
The morphinane-derivate 6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([(18)F]FDPN) is a nonselective opioid receptor ligand currently used in positron emission tomography (PET). Correction for plasma metabolites of the arterial input function is necessary for quantitative measurements of [(18)F]FDPN binding. A study was undertaken to investigate if there are gender dependent differences in the rate of metabolism of [(18)F]FDPN.


METHODS
The rate of metabolism of [(18)F]FDPN was mathematically quantified by fitting a bi-exponential function to each individual's dynamic metabolite data.


RESULTS
No statistically significant gender differences were found for age, weight, body mass index or dose. However, significant differences (p < 0.01) in two of the four kinetic parameters describing the rate of metabolism were found between the two groups, with women metabolizing [(18)F]FDPN faster than men. These differences were found in the contribution of the fast and slow kinetic components of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of [(18)F]FDPN in women than in men.


CONCLUSIONS
The findings reinforce the need for individualized metabolite correction during [(18)F]FDPN-PET scans and also indicate that in certain cases, grouping according to gender could be performed in order to minimize methodological errors of the input function prior to kinetic analyses.
Henriksen
G
G
Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany. G.Henriksen@lrz.tum.de
Spilker
M E
ME
Sprenger
T
T
Hauser
A I
AI
Platzer
S
S
Boecker
H
H
Toelle
T R
TR
Schwaiger
M
M
Wester
H-J
HJ
D000328:Adult; D004174:Diprenorphine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D012727:Sex Characteristics
C411951:6-O-(2-(18F)fluoroethyl)-6-O-desmethyldiprenorphine; D004174:Diprenorphine