Background: To investigate dynamic live tissue organophosphorus nerve agent
uptake and distribution fates resulting in acetylcholinesterase inhibition, we recently reported
the first-in-class fluorine-18 [18F] radiolabeled Positron Emission Tomography (PET) imaging
tracer known as [18F]O-(2-fluoroethyl)-O-(p-nitrophenyl)methylphosphonate. This tracer
has been initially studied in live rats with PET imaging.
Objective: We sought to evaluate the PET tracer in vivo using a new dose formulation of saline,
ethanol and L-ascorbic acid, and compare the influence of this formulation on in vivo
tracer performance to previous data collected using a CH3CN:PBS formulation.
Methods: A high molar activity [18F]tracer radiosynthesis was used. Doses were formulated
as saline, ethanol (≤ 1%) and L-ascorbic acid (0.1%), pH 4.0-4.5. Stability was evaluated to 6
h. Dose injection (i.v.) into male rats was followed by either ex vivo biodistribution profiling
at 5, 30, 90 min, or dynamic 90 min PET imaging. Rat biodistribution and PET imaging data
Results and Discussion: An optimized radiosynthesis (8 ± 2 % RCY) resulted in stable
doses for 6 h (>99%). Arterial blood included a tracer and a single metabolite. The ex vivo
biodistribution and live tissue PET imaging data revealed rapid radioactivity uptake and distributed
tissue levels: heart and lung, highest; liver, moderate; and brain, lowest.
Conclusion: Imaging and biodistribution data were highly correlated with expected radioactivity
tissue uptake and distribution in target organs. Lower brain radioactivity levels by PET
imaging were found for the new formulation (saline, 1% L-ascorbic acid, < 1% ethanol) as
compared to the established CH3CN:PBS formulation. Overall, we found that the i.v. dose
formulation changed the in vivo profile of an organophosphorus PET tracer that is considered
an important finding for future organophosphorus PET tracer studies.