TY - JOUR
T1 - Real-Time Interrogation of Aspirin Reactivity, Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy
AU - Zacharias, Niki M.
AU - Ornelas, Argentina
AU - Lee, Jaehyuk
AU - Hu, Jingzhe
AU - Davis, Jennifer S.
AU - Uddin, Nasir
AU - Pudakalakatti, Shivanand
AU - Menter, David G.
AU - Karam, Jose A.
AU - Wood, Christopher G.
AU - Hawk, Ernest T.
AU - Kopetz, Scott
AU - Vilar, Eduardo
AU - Bhattacharya, Pratip K.
AU - Millward, Steven W.
N1 - Funding Information:
This work was supported by MD Anderson start-up funds (S.W.M., P.B.), R21CA181994 (S.W.M.), 2R44CA206771 (S.W.M.), R21CA185536 (P.B.), CPRIT RP180164 (P.B.), CDMRP PC110065 (N.Z., J.L., P.B.), Colleen≫s Dream Foundation (NZ), an MD Anderson Institutional Research Grant (N.Z., P.B.), and a grant from the Gulf Coast Consortium (J.L., P.B.). Additional funding was provided by a GE In-kind Multi-investigator Imaging (MI2) Research Award (S.W.M., P.B.), the Boone Pickens Distinguished Chair for Early Prevention of Cancer, The Duncan Family Institute for Cancer Prevention and Risk Assessment, the Colorectal Moon Shot, 1R01CA187238, 5R01CA1722670, and 1R01CA184843. A.O. was supported by a cancer prevention educational award (R25T CA057730, Dr. Shine Chang, PI). S.P. was supported by Gulf Coast Consortia/Keck Center postdoctoral fellowship CPRIT RP170593. The MD Anderson Nuclear Magnetic Resonance Facility and Small Animal Imaging Facility (SAIF) are supported by the MD Anderson Cancer Center Support Grant 5P30CA016672 (Dr. Peter Pisters). We also thank the staff at the SAIF and the NMR facility for their assistance with the magnetic resonance imaging experiments and the Department of Scientific Publications at MD Anderson Cancer Center for reading and editing this manuscript.
Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/3/22
Y1 - 2019/3/22
N2 - Hyperpolarized magnetic resonance spectroscopy enables quantitative, non-radioactive, real-time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single- and double- 13 C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T 1 ) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13 C-NMR spectroscopy. Hyperpolarized, double-labeled aspirin was well tolerated in mice and could be observed by both 13 C-MR imaging and 13 C-NMR spectroscopy in vivo.
AB - Hyperpolarized magnetic resonance spectroscopy enables quantitative, non-radioactive, real-time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single- and double- 13 C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T 1 ) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13 C-NMR spectroscopy. Hyperpolarized, double-labeled aspirin was well tolerated in mice and could be observed by both 13 C-MR imaging and 13 C-NMR spectroscopy in vivo.
KW - aspirin
KW - chemopreventive
KW - hyperpolarization
KW - magnetic resonance imaging
KW - magnetic resonance spectroscopy
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U2 - 10.1002/anie.201812759
DO - 10.1002/anie.201812759
M3 - Article
C2 - 30680862
AN - SCOPUS:85061798975
SN - 1433-7851
VL - 58
SP - 4179
EP - 4183
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 13
ER -