Non-invasive diagnostic imaging technology for mitochondria using radiolabeled lipophilic salts
The invention provides lipophilic salts, particularly, lipophilic salts comprising a pharmaceutically acceptable anion and at least one phosphonium or ammonium cation. In certain embodiments, the cation is labeled with one or more radioisotopes. The lipophilic salts of the invention exhibit an affinity for dysfunctional mitochondria, and are useful for the imaging of cardiovascular diseases and disorders. The invention also provides pharmaceutical compositions and methods of using the lipophilic salts.
1. A method of imaging cardiac infarction, cardiac perfusion, heart failure, cardiomyopathy or ischemia comprising:
providing a radiolabeled salt comprising at least one pharmaceutically acceptable anion and 18 F-4-fluorobenzyl-triphenylphosphonium ion;
contacting cells or tissues in a subject with the radiolabeled salt; and
making a radiographic image.
2. The method of claim 1 , wherein the image correlates with mitochondrial membrane potential (ΔΨm).
3. The method of claim 2 , wherein the image correlates with suppressed or enhanced apoptosis.
4. The method of claim 1 , wherein the image correlates with imaging mitochondrial dysfunction.
5. The method of claim 1 , wherein the radiolabeled salt exhibits a target to non-target ratio of at least about 5:1.
6. The method of claim 1 , wherein the radiolabeled salt is stable in vivo.
7. The method of claim 1 , wherein the radiolabeled salt substantially localizes to a site or sites having dysfunctional mitochondria within about 120 minutes after administration.
8. The method of claim 1 , wherein the radiolabeled salt substantially localizes to a site or sites dysfunctional mitochondria within about 60 minutes after administration.
9. The method of claim 1 , wherein the radiolabeled salt substantially localizes to a site or sites dysfunctional mitochondria within about 30 minutes after administration.
10. The method of claim 1 , wherein the radiolabeled salt is detected by a gamma camera, positron emission tomography (PET) or single photon emission tomography (SPECT).
11. The method of claim 1 , wherein the subject is a human, rat, mouse, cat, dog, horse, sheep, cow, monkey, avian, or amphibian.
12. The method of claim 1 , wherein the cell is a myocyte.
13. The method of any one of claims 7 - 9 , wherein the site or sites are in the myocardium.