In Vivo Mitochondrial Labeling Using Positively-Charged Nitroxide Enhanced and Gadolinium Chelate Enhanced Magnetic Resonance Imaging
AssigneeThe Medical College of Wisconsin Research Foundation, Inc.
InventorsBalaraman Kalyanaraman, Joy Joseph, Kathleen Marie Schmainda, Douglas Edward Prah, Marcos Lopez, Micael J. Hardy
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Abstract
A system and method for acquiring MR imaging data from a subject includes administering positively-charged nitroxides or gadolinium chelates for in vivo mitochondrial labeling, acquiring MR imaging data from the subject, and reconstructing an image of the subject having enhanced contrast in areas including metabolic and/or mitotic activity.
Claims24
A method of in vivo MR imaging a target area of a subject comprising the steps of:
- a) administering a mitochondria-targeted contrast agent to the subject;
- b) applying a pulse sequence selected to acquire MR imaging data from the target area of the subject;
- and
- c) reconstructing an image of the target area of the subject having enhanced contrast in areas of at least one of metabolic and mitotic activity.
A mitochondria-targeted contrast agent molecule, comprising:
- a) a gadolinium (III) ion bound to a hexadentate, heptadentate, octadentate, or nonadentate organic chelating agent;
- b) a triphenylphosphonium group;
- and
- c) a phenylthiocarbamide linking group coupling the triphenylphosphonium group to the organic chelating agent.
A compound having the formula:
- wherein L is a paramagnetic metal selected from Cr, Mn, Fe, Co, Ni, Cu, Pr, Nd, Sm, Y, Gd, Tb, Dy, Nd, Pm, Ho, Sm, Tm, Eu, Yb, Lu or Er;
- wherein R1 is S, N or P,
- wherein R2 is a branched or straight chain, saturated or unsaturated, substituted or unsubstituted C1-25 group,
- wherein R3 is a branched or straight chain, saturated or unsaturated, substituted or unsubstituted organic chelating moiety comprising one or more of carboxyl, amine, amide, ester, alcohol or thiol,
- wherein R4, R5 or R6 are the same or independently a straight or branched, saturated or unsaturated, substituted or unsubstituted C1-10 alkyl or cycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl, and
- wherein X− is Cl−, I−, Fl− or another salt-forming counterion, or a solvate or hydrate thereof.
A compound made by the steps of:
- (a) providing a compound having the formula:
- wherein R1 is S, N or P,
- wherein R2 is branched or straight chain, saturated or unsaturated, substituted or unsubstituted C1-25 group,
- wherein R3 is a branched or straight chain, saturated or unsaturated, substituted or unsubstituted organic chelating moiety comprising one or more of carboxyl, amine, amide, ester, alcohol or thiol,
- wherein R4, R5 or R6 are the same or independently a straight or branched, saturated or unsaturated, substituted or unsubstituted C1-10 alkyl or cycloalkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl, and,
- wherein X− is Cl−, I−, Fl− or another salt-forming counterion,
- or a solvate or hydrate thereof, and
- (b) chelating the compound by contacting the compound with a paramagnetic metal selected from Cr, Mn, Fe, Co, Ni, Cu, Pr, Nd, Sm, Y, Gd, Tb, Dy, Nd, Pm, Ho, Sm, Tm, Eu, Yb, Lu or Er.
Dependencies are inferred from the claim text.