Non-invasive diagnostic imaging technology for mitochondria dysfunction using radiolabeled lipophilic salts
AssigneeThe Johns Hopkins University
InventorsIgal Madar, Hayden T. Ravert, Robert Francis Dannals, Ursula A. Scheffel, James J. Frost
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Abstract
The invention provides a series of lipophilic phosphonium cations (PhCs) labeled with 18F for non-invasive assessment of ΔΨm, lipophilic ammonium cation analogs of the PhCs, and methods of using same for imaging and detection of mitochondrial-related pathologies in patients using PET or SPECT.
Claims20
A compound comprising at least one pharmaceutically acceptable anion and a cation represented by the following formula:
- wherein
- R1 is alkyl, alkenyl, alkynyl, haloalkyl, cycloalkyl, or aralkyl, with R1 being substituted by one or more groups comprising 18F and optionally substituted by one or more additional groups;
- R2, R3, and R4 are independently selected at each occurrence of R2, R3, and R4 from the group consisting of hydrogen, halogen, cyano, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted alkoxy, optionally substituted (cycloalkyl)alkyl, optionally substituted alkyithio, optionally substituted alkylsulfinyl, or optionally substituted alkylsulfonyl, and optionally substituted mono or dialkylcarboxamide;
- and
- p, q, and r are independently selected numbers from zero to 5.
A compound comprising at least one pharmaceutically acceptable anion and a cation represented by the following formula:
- wherein
- Ar1, Ar2, and Ar3 are independently selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, and optionally substituted aralkyl;
- and
- m is an integer of to 1 to 5.
A compound which selected from the group consisting of:
- 18F-4-fluorobenzyl-triphenylphosphonium;
- 18F-2-fluorobenzyl-triphenylphosphonium;
- or
- 18F-3-fluorobenzyl-triphenylphosphonium.
A compound selected from the group consisting of
- 18F-2-fluoroethyl-triphenylphosphonium;
- 18F-2-fluoroethyl-tri-ortho-tolylphosphonium;
- 18F-2-fluoroethyl-tri-meta-tolylphosphonium;
- 18F-2-fluoroethyl-tri-para-tolylphosphonium;
- 18F-3-fluoropropyl-triphenylphosphonium;
- 18F-3-fluoropropyl-tri-ortho-tolylphosphonium;
- 18F-3-fluoropropyl-tri-meta-tolylphosphonium;
- 18F-3-fluoropropyl-tri-para-tolylphosphonium;
- 18F-4-fluorobutyl-triphenylphosphonium;
- 18F-4-fluorobutyl-tri-ortho-tolylphosphonium;
- 18F-4-fluorobutyl-tri-meta-tolylphosphonium;
- 18F-4-fluorobutyl-tri-para-tolylphosphonium;
- 18F-2-fluorobenzyl-tri-ortho-tolylphosphonium;
- 18F-2-fluorobenzyl-tri-meta-tolylphosphonium;
- 18F-2-fluorobenzyl-tri-para-tolylphosphonium;
- 18F-3-fluorobenzyl-tri-ortho-tolylphosphonium;
- 18F-3-fluorobenzyl-tri-meta-tolylphosphonium;
- 18F-3-fluorobenzyl-tri-para-tolylphosphonium;
- 18F-4-fluorobenzyl-tri-ortho-tolylphosphonium;
- 18F-4-fluorobenzyl-tri-meta-tolylphosphonium;
- 18F-4-fluorobenzyl-tri-para-tolylphosphonium;
- 18F-3-fluoro-4-formyl-benzyl-triphenylphosphonium;
- 18F-3-fluoro-4-formyl-benzyl-tri-ortho-tolylphosponium;
- 18F-3-fluoro-4-formyl-benzyl-tri-meta-tolylphosphonium;
- 18F-3-fluoro-4-formyl-benzyl-tri-para-tolylphosphonium;
- (18F-4-fluorobenzyl)-(2-chloroethyl)-diphenylphosphonium;
- (18F-4-fluorobenzyl)-(3-chloropropyl)-diphenylphosphonium;
- (18F-4-fluorobenzyl)-(4-chlorobutyl)-diphenylphosphonium;
- (18F-4-fluorobenzyl)-(6-chloropentyl)-diphenylphosphonium;
- (18F-4-fluorobenzyl)-(5-chlorohexyl)-diphenylphosphonium;
- 18F-2-fluoroethyl-tri(4-pyridyl)phosphonium;
- 18F-3-fluoropropyl-tri(4-pyridyl)phosphonium;
- 18F-4-fluorobutyl-tri(4-pyridyl)phosphonium;
- 18F-2-fluorobenzyl-tri(4-pyridyl)phosphonium;
- 18F-3-fluorobenzyl-tri(4-pyridyl)phosphonium;
- 18F-4-fluorobenzyl-tri(4-pyridyl)phosphonium;
- or
- 18F-3-fluoro-4-formyl-benzyl-tri(4-pyridyl)phosphonium.
Dependencies are inferred from the claim text.