TY - JOUR
T1 - Optimized and automated radiosynthesis of [18F]DHMT for translational imaging of reactive oxygen species with positron emission tomography
AU - Zhang, Wenjie
AU - Cai, Zhengxin
AU - Li, Lin
AU - Ropchan, Jim
AU - Lim, Keunpoong
AU - Boutagy, Nabil E.
AU - Wu, Jing
AU - Stendahl, John C.
AU - Chu, Wenhua
AU - Gropler, Robert
AU - Sinusas, Albert J.
AU - Liu, Chi
AU - Huang, Yiyun
N1 - Funding Information:
The authors are grateful for the financial support provided by internal funding from Yale, and NIH grants R01HL123949 and T32HL098069.
Publisher Copyright:
© 2016 by the authors; licensee MDPI.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these diseases. For the purpose of clinical translation of [18F]6-(4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-methyl-5,6-dihydrophenanthridine-3,8-diamine ([18F]DHMT), a promising ROS PET radiotracer, we first manually optimized the large-scale radiosynthesis conditions and then implemented them in an automated synthesis module. Our manual synthesis procedure afforded [18F]DHMT in 120 min with overall radiochemical yield (RCY) of 31.6% ± 9.3% (n = 2, decay-uncorrected) and specific activity of 426 ± 272 GBq/μmol (n = 2). Fully automated radiosynthesis of [18F]DHMT was achieved within 77 min with overall isolated RCY of 6.9% ± 2.8% (n = 7, decay-uncorrected) and specific activity of 155 ± 153 GBq/μmol (n = 7) at the end of synthesis. This study is the first demonstration of producing 2-[18F]fluoroethyl azide by an automated module, which can be used for a variety of PET tracers through click chemistry. It is also the first time that [18F]DHMT was successfully tested for PET imaging in a healthy beagle dog.
AB - Reactive oxygen species (ROS) play important roles in cell signaling and homeostasis. However, an abnormally high level of ROS is toxic, and is implicated in a number of diseases. Positron emission tomography (PET) imaging of ROS can assist in the detection of these diseases. For the purpose of clinical translation of [18F]6-(4-((1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-5-methyl-5,6-dihydrophenanthridine-3,8-diamine ([18F]DHMT), a promising ROS PET radiotracer, we first manually optimized the large-scale radiosynthesis conditions and then implemented them in an automated synthesis module. Our manual synthesis procedure afforded [18F]DHMT in 120 min with overall radiochemical yield (RCY) of 31.6% ± 9.3% (n = 2, decay-uncorrected) and specific activity of 426 ± 272 GBq/μmol (n = 2). Fully automated radiosynthesis of [18F]DHMT was achieved within 77 min with overall isolated RCY of 6.9% ± 2.8% (n = 7, decay-uncorrected) and specific activity of 155 ± 153 GBq/μmol (n = 7) at the end of synthesis. This study is the first demonstration of producing 2-[18F]fluoroethyl azide by an automated module, which can be used for a variety of PET tracers through click chemistry. It is also the first time that [18F]DHMT was successfully tested for PET imaging in a healthy beagle dog.
KW - 2-[F]fluoroethyl azide
KW - Automation
KW - In vivo imaging
KW - PET
KW - Reactive oxygen species
KW - Translational study
UR - http://www.scopus.com/inward/record.url?scp=85007146535&partnerID=8YFLogxK
U2 - 10.3390/molecules21121696
DO - 10.3390/molecules21121696
M3 - Article
C2 - 27941676
AN - SCOPUS:85007146535
SN - 1420-3049
VL - 21
JO - Molecules
JF - Molecules
IS - 12
M1 - 1696
ER -