Optimization of Automated 18F Fluoroalkylation : Production of 3 Opioid PET Tracers

Abstract

PET is an effective tool for imaging of biochemical processes within patients and is instrumental for quantitative imaging of the availability of opioid receptors in the central nervous system. The opioid receptor system is involved in many important pathologic processes within the body such as processing of pain and immunological responses. This master thesis contributes to the availability of PET tracers for the opioid receptor system by devising a 3-step, 2-pot automated method for synthesis of three 18F-labeled opioid receptor system PET tracers. In addition to opioid receptor system PET tracers, this method can be used to label other PET tracers by [18F]fluoroalkylation. The three opioid receptor system tracers produced in this study: 6-O-[18F]Fluoroethyl-6-O-desmethyl-diprenorphine, 6-O-[18F]Fluoroethyl-6-O-desmethyl-buprenorphine, and 6-O-[18F]Fluoroethyl-6-O-desmethyl-phenylethylorvinol are synthesized by automation for the first time on the same automated module. Automated production of the 3 structurally related opioid receptor system PET tracers allows for investigations of antagonist versus agonist properties previously impossible. Automation also allows for production of PET tracers under “Good Manufacturing Practice” (GMP) guidelines, decreases synthesis times, increases yields and quality, increases reproducibility, and increases the availability of PET tracers while lowering their cost of production.