P-Glycoprotein (P-gp) overexpression has been observed in several cancer types and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. P-gp has become an attractive target for molecular imaging of cancer and brain diseases using biomedical imaging technique positron emission tomography (PET). Several PET radioligands have been investigated for their feasibilities to visualize P-gp at the blood-brain barrier (BBB). [11C]N-desmethyl-loperamide ([11C]dLop) is one of the promising candidates progressing to human PET studies, which is derived from the parent radiotracer [11C]loperamide and originally developed and characterized at the National Institute of Mental Health. Here we present a high-yield synthesis of [11C]dLop and [11C]loperamide. N-Desmethyl-loperamide and loperamide were synthesized from a,a-diphenyl-?-butyrolactone and 4-(4-chlorophenyl)-4-hydroxypiperidine in 5 and 4 steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2-diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21-57% overall yield. [11C]dLop and [11C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [11C]CH3OTf through N-[11C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [11C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/�mol specific activity at EOB.

High-yield synthesis of P-glycoprotein radioligands [11C]N-desmethyl-loperamide and [11C]loperamide

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.