[11C]GR103545: novel one-pot radiosynthesis with high specific activity

Area of Science:

• Radiochemistry
• Neuroscience
• Medical Imaging

Background:

• GR103545 is a selective kappa-opioid receptor agonist with potential for positron emission tomography (PET) imaging.
• Previous [(11)C]GR103545 synthesis yielded low specific activity (SA), limiting human studies due to potential physiological side effects from injected mass.
• A need existed for an improved radiosynthesis to enable clinical translation.

Purpose of the Study:

• To develop an alternative radiosynthesis for [(11)C]GR103545 with enhanced specific activity (SA) and radiochemical yields.
• To overcome limitations of previous synthesis methods for human PET imaging applications.

Main Methods:

• A two-step, one-pot automated synthesis using the TRACERLab FXC module.
• Transcarboxylation of a precursor to form a carbamic acid intermediate.
• [(11)C]methylation of the intermediate using [(11)C]methyl trifluoromethanesulfonate for radiolabeling.

Main Results:

• The novel synthesis achieved ≥90% chemical and radiochemical purity for [(11)C]GR103545.
• Resulting specific activity (SA) was 290.45±99.9 MBq/nmol.
• Average synthesis time was 43 minutes with high injectable radioactivity.

Conclusions:

• A practical, one-pot method for routine production of [(11)C]GR103545 was successfully developed.
• The method reliably produces high SA and radiochemical yields, suitable for human imaging.
• This advancement permits the use of [(11)C]GR103545 as a PET tracer in human studies.