Journal article
Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)
EJNMMI radiopharmacy and chemistry, v 5(1), pp 1-15
31 Dec 2019
PMID: 31893318
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background
Conventional scale production of small batches of PET tracers (e.g. for preclinical imaging) is an inefficient use of resources. Using O-(2-[
18
F]fluoroethyl)-L-tyrosine ([
18
F]FET), we demonstrate that simple microvolume radiosynthesis techniques can improve the efficiency of production by consuming tiny amounts of precursor, and maintaining high molar activity of the tracers even with low starting activity.
Procedures
The synthesis was carried out in microvolume droplets manipulated on a disposable patterned silicon “chip” affixed to a heater. A droplet of [
18
F]fluoride containing TBAHCO
3
was first deposited onto a chip and dried at 100 °C. Subsequently, a droplet containing 60 nmol of precursor was added to the chip and the fluorination reaction was performed at 90 °C for 5 min. Removal of protecting groups was accomplished with a droplet of HCl heated at 90 °C for 3 min. Finally, the crude product was collected in a methanol-water mixture, purified via analytical-scale radio-HPLC and formulated in saline. As a demonstration, using [
18
F]FET produced on the chip, we prepared aliquots with different molar activities to explore the impact on preclinical PET imaging of tumor-bearing mice.
Results
The microdroplet synthesis exhibited an overall decay-corrected radiochemical yield of 55 ± 7% (
n
= 4) after purification and formulation. When automated, the synthesis could be completed in 35 min. Starting with < 370 MBq of activity, ~ 150 MBq of [
18
F]FET could be produced, sufficient for multiple in vivo experiments, with high molar activities (48–119 GBq/μmol). The demonstration imaging study revealed the uptake of [
18
F]FET in subcutaneous tumors, but no significant differences in tumor uptake as a result of molar activity differences (ranging 0.37–48 GBq/μmol) were observed.
Conclusions
A microdroplet synthesis of [
18
F]FET was developed demonstrating low reagent consumption, high yield, and high molar activity. The approach can be expanded to tracers other than [
18
F]FET, and adapted to produce higher quantities of the tracer sufficient for clinical PET imaging.
Metrics
Details
- Title
- Rapid, efficient, and economical synthesis of PET tracers in a droplet microreactor: application to O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET)
- Creators
- Ksenia Lisova - University of California, Los AngelesBao Ying Chen - University of California, Los AngelesJia Wang - University of California, Los AngelesKelly Mun-Ming Fong - University of California, Los AngelesPeter M. Clark - University of California, Los AngelesR. Michael van Dam - University of California, Los Angeles
- Publication Details
- EJNMMI radiopharmacy and chemistry, v 5(1), pp 1-15
- Publisher
- Springer International Publishing
- Grant note
- T32 EB002101 / National Institute of Biomedical Imaging and Bioengineering (http://dx.doi.org/10.13039/100000070) R21 AG049918 / National Institute on Aging (http://dx.doi.org/10.13039/100000049) R44 MH 097271 / National Institute of Mental Health (http://dx.doi.org/10.13039/100000025) R21 CA212718; P30 CA016042 / National Cancer Institute (http://dx.doi.org/10.13039/100000054)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; Drexel University
- Web of Science ID
- WOS:000667948700001
- Scopus ID
- 2-s2.0-85088302642
- Other Identifier
- 991019356496004721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Chemistry, Inorganic & Nuclear
- Chemistry, Medicinal
- Radiology, Nuclear Medicine & Medical Imaging