Modulation of CEST images in vivo by T1 relaxation: a new approach in the design of responsive PARACEST agents.
A novel approach for the design of responsive paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance imaging (MRI) agents has been developed where the signal is "turned on" by altering the longitudinal relaxation time (T1) of bulk water protons. To demonstrate this approach, a model Eu(DOTA-tetraamide) complex (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) containing two nitroxide free radical units was synthesized. The nitroxide groups substantially shortened the T1 of the bulk water protons which, in turn, resulted in quenching of the CEST signal. Reduction of paramagnetic nitroxide moieties to a diamagnetic species resulted in the appearance of CEST. The modulation of CEST by T1 relaxation provides a new platform for designing biologically responsive MRI agents.
Advanced Imaging Research Center, UT Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
S James
SJ
Ratnakar
Todd C
TC
Soesbe
Lloyd Laporca
LL
Lumata
Quyen N
QN
Do
Subha
S
Viswanathan
Chien-Yuan
CY
Lin
A Dean
AD
Sherry
Zoltan
Z
Kovacs
D000818:Animals; D003287:Contrast Media / Q000737:chemistry*; D015195:Drug Design; D005260:Female; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D060328:Magnetic Phenomena; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D010084:Oxidation-Reduction; D011522:Protons; D013997:Time Factors; D014867:Water / Q000737:chemistry
D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D011522:Protons; D014867:Water; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid