6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([(18)F]FDPN) is a nonselective opiate ligand that binds to postsynaptic micro, kappa and delta opiate receptors. Due to the longer half-life of F-18, compared to C-11, labeling DPN with F-18 allows for alternative experimental protocols and potentially the evaluation of endogenous opioid release. The applicability of this compound to assorted experimental protocols motivated the evaluation of [(18)F]FDPN kinetics with compartmental and non-compartmental models. The results indicate that a two-tissue compartmental model best characterizes the data obtained following a bolus injection of [(18)F]FDPN (120-min scanning protocol). Estimates of distribution volume (DV) were robust, being highly correlated for the one-tissue compartmental model as well as the invasive Logan model and the basis function method. Furthermore, the DV estimates were also stable under a shortened protocol of 60 min, showing a significant correlation with the full protocol. The binding potential (BP) values showed more variability between methods and in some cases were more sensitive to protocol length. In conclusion, this evaluation of [(18)F]FDPN kinetics illustrates that DV values can be estimated robustly using compartmental modeling, the basis function method or the invasive Logan modeling approach on a volume of interest level. BP values were also found to correlate with DV values; however, these results should be interpreted with the understanding that specific binding in the reference region (occipital region) may exist.