Performing radiosynthesis in microvolumes to maximize molar activity of tracers for positron emission tomography

Maxim Sergeev,Federica Morgia,Pei Yuin Keng,Mark Lazari,Jeffrey Collins,Jason T Lee,Jason Jones,Olga Sergeeva,Muhammad Rashed Javed,Michael E Phelps,R Michael Van Dam

doi:10.1038/s42004-018-0009-z

Abstract

Positron emission tomography (PET) is a molecular diagnostic imaging technology to quantitatively visualize biological processes in vivo. For many applications, including imaging of low-tissue density targets (e.g., neuroreceptors), imaging in small animals, and evaluation of novel tracers, the injected PET tracer must be produced with high molar activity to ensure low occupancy of biological targets and avoid pharmacologic effects. Additionally, high molar activity is essential for tracers with lengthy syntheses or tracers transported to distant imaging sites. Here we show that radiosynthesis of PET tracers in microliter volumes instead of conventional milliliter volumes results in substantially increased molar activity, and we identify the most relevant variables affecting this parameter. Furthermore, using the PET tracer [18F]fallypride, we illustrate that molar activity can have a significant impact on biodistribution. With full automation, microdroplet platforms could provide a means for radiochemists to routinely, conveniently, and safely produce PET tracers with high molar activity.

Highlights

Positron emission tomography (PET) is a molecular diagnostic imaging technology to quantitatively visualize biological processes in vivo
During synthesis of PET tracers, inevitable contamination by sources of non-radioactive [19F]fluoride leads to a final product comprising a mixture of 18F- and 19F-labeled molecules, of which only the former are detectable by the PET scanner
PET “microdosing” studies to evaluate the pharmacokinetics of novel drug compounds[22,23,24,25], extends the distance/time over which tracers can be transported to the imaging site[26], and is critical in preclinical research, where much higher concentrations of the tracer per mass of the animal must be injected to achieve sufficient signal-to-noise ratio[19, 20, 27]

Summary

Introduction

Positron emission tomography (PET) is a molecular diagnostic imaging technology to quantitatively visualize biological processes in vivo. For many applications, including imaging of low-tissue density targets (e.g., neuroreceptors), imaging in small animals, and evaluation of novel tracers, the injected PET tracer must be produced with high molar activity to ensure low occupancy of biological targets and avoid pharmacologic effects. PET applications span a broad range of medical fields, including oncology, cardiology, immunology, and neurology. In the latter, for example, PET is used in the diagnosis and monitoring of neurodegenerative disorders[6], and is a vital tool in the discovery and development of novel therapeutics by enabling in situ measurements of drug target occupancy, binding kinetics, etc.[7]. PET “microdosing” studies to evaluate the pharmacokinetics of novel drug compounds[22,23,24,25], extends the distance/time over which tracers can be transported to the imaging site[26], and is critical in preclinical research, where much higher concentrations of the tracer per mass of the animal must be injected (compared to humans) to achieve sufficient signal-to-noise ratio[19, 20, 27]

Methods

Results

Conclusion