Positron emission tomography (PET) using the radiotracer [18F]-FDOPA provides a tool for studying brain dopamine synthesis
capacity in animals and humans. We have previously standardised a micro-PET methodology in mice by intravenously
administering [18F]-FDOPA via jugular vein cannulation and assessment of striatal dopamine synthesis capacity, indexed as the
influx rate constant Ki
Mod of [18F]-FDOPA, using an extended graphical Patlak analysis with the cerebellum as a reference region.
This enables a direct comparison between preclinical and clinical output values. However, chronic intravenous catheters are
technically difficult to maintain for longitudinal studies. Hence, in this study, intraperitoneal administration of [18F]-FDOPA was
evaluated as a less-invasive alternative that facilitates longitudinal imaging. Our experiments comprised the following assessments:
(i) comparison of [18F]-FDOPA uptake between intravenous and intraperitoneal radiotracer administration and optimisation of
the time window used for extended Patlak analysis, (ii) comparison of KiMod in a within-subject design of both administration
routes, (iii) test-retest evaluation of KiMod in a within-subject design of intraperitoneal radiotracer administration, and (iv)
validation of KiMod estimates by comparing the two administration routes in a mouse model of hyperdopaminergia induced by
subchronic ketamine. Our results demonstrate that intraperitoneal [18F]-FDOPA administration resulted in good brain uptake,
with no significant effect of administration route on KiMod estimates (intraperitoneal: 0:024 ± 0:0047 min−1, intravenous: 0:022 ±
0:0041 min−1, p = 0:42) and similar coefficient of variation (intraperitoneal: 19.6%; intravenous: 18.4%). The technique had a
moderate test-retest validity (intraclass correlation coefficientðICCÞ = 0:52, N = 6) and thus supports longitudinal studies.
Following subchronic ketamine administration, elevated Ki
Mod as compared to control condition was measured with a large
effect size for both methods (intraperitoneal: Cohen’s d = 1:3; intravenous: Cohen’s d = 0:9), providing further evidence that
ketamine has lasting effects on the dopamine system, which could contribute to its therapeutic actions and/or abuse liability.