18F-labelled N,N-dimethylamphetamine analogues for brain imaging studies

Area of Science:

• Radiochemistry and Nuclear Medicine
• Organic Synthesis
• Pharmacology

Background:

• Development of novel radiotracers is crucial for advancing molecular imaging techniques.
• Amphetamine analogues are investigated for their potential in positron emission tomography (PET) imaging.
• Efficient radiofluorination methods are needed for synthesizing [18F]-labeled compounds.

Purpose of the Study:

• To determine the radiochemical yields of novel N,N-dimethyl-2-(substituted phenyl)-isopropylamines (amphetamine analogues) using [18F]acetyl hypofluorite.
• To evaluate the purification efficiency and time for the synthesized [18F]-labeled amphetamines.
• To assess the in vivo brain and lung uptake characteristics of a specific analogue, 5-[18F]-2,4-Dimethoxy-N,N-dimethylamphetamine (5-[18F]-2,4-DNNA), using PET imaging.

Main Methods:

• Radiosynthesis of nine amphetamine analogues via reaction with [18F]acetyl hypofluorite in 0.1 M HCl.
• Purification of [18F]-labeled products using chromatographic techniques.
• Positron emission tomography (PET) studies in a canine model to evaluate brain and lung uptake dynamics of 5-[18F]-2,4-DNNA.

Main Results:

• The meta-dimethoxy substituted amphetamines yielded the highest radiofluorination efficiency (24-32% at end-of-beam).
• Purification of the [18F]-labeled amphetamines was accomplished within 10-20 minutes.
• In vivo PET imaging revealed that 5-[18F]-2,4-DNNA exhibited lower initial brain uptake and faster radioactivity clearance compared to its iodinated analogue.

Conclusions:

• The developed radiofluorination method is effective for synthesizing [18F]-labeled amphetamine analogues.
• Meta-dimethoxy substitution enhances radiofluorination yields for this class of compounds.
• 5-[18F]-2,4-DNNA shows distinct pharmacokinetic properties in the brain, suggesting potential for specific imaging applications.