Aim
To address the question of whether gender related differences exist in the metabolism rate of (F-18)FDPN and comment on its potential implications for design and analysis of future PET studies.
Methods
6-O-(2-F-18-fluoroethyl)-6-O-desmethyldiprenorphine ((F-18)FDPN) is a non-selective opioid receptor ligand frequently used in positron emission tomography (PET). Experimental studies show that there are sex dependent differences in opioid analgesia which may be, at least in part, due to gender differences in the activity of the enzymes responsible for metabolizing opioids. In order to investigate potential gender dependent differences in the metabolism rate of (F-18)FDPN, 19 healthy volunteers were included in this study (9 females and 10 males; mean age of 42 +/− 12 years). The fraction of intact (F-18)FDPN present in plasma was determined by reverse-phase HPLC. A corrected plasma input function was generated on the basis of these HPLC data which in advance were corrected for recovery of radioactivity from plasma. The rate of metabolism of (F-18)FDPN was mathematically quantified by using a bi-exponential function (Aexp(-a × t) + Bexp(-b × t)) to the individual dynamic metabolite data.
Results
Statistically significant gender differences in the input finction were not found for age, weight, body-mass-index, and dose. However, significant differences (p < 0.01) in two of the four kinetic parameters (A, B, a, b) describing the rate of metabolism were found between the two groups, with female subjects metabolizing (F-18)FDPN faster than males. These differences were found in the contribution of the fast and slow kinetic components (A and B) of the model describing the distribution of radioactive species in plasma, indicating a higher rate of enzyme-dependent degradation of (F-18)FDPN in females than in males.
Conclusion
Gender dependent classification of subjects included in PET studies with (F-18)FDPN might influence data analysis and experimental protocols. Our findings reinforce the need for individualized metabolite correction during (F-18)FDPN scans. In certain cases, where grouping of subjects is used to generate a normalized reference plasma input function, only gender specific grouping will give valid estimates.