Cancer diagnosis and imaging
View Patent ↗The present invention provides a method for imaging a disease or condition in a mammal which includes the steps of; administering a therapeutically effective amount of a cell cycle inhibitor to effectively stop proliferation of eukaryotic cells at a cell cycle checkpoint between the G1 and S phase, stopping administration of the cell cycle inhibitor for a period of time, administering a marker to the mammal and imaging the mammal.
1. A method for increasing the sensitivity of imaging a cancerous or pre-cancerous disease in a mammal which comprises the steps of:
(a) administering to the mammal an effective amount of a T-type calcium channel inhibitor that inhibits proliferation of cancerous or pre-cancerous diseased cells by inhibiting cell cycle progression through the checkpoint between the G1 and S phase wherein the diseased cells accumulate at the G1/S checkpoint of the cell cycle;
(b) subsequently administering an imaging marker to the mammal after a period wherein cells that have accumulated at the G1/S checkpoint of the cell cycle following administration of the T-type calcium channel inhibitor have progressed to the S phase of the cell cycle, resulting in an increased proportion of the diseased cells in the S phase of the cell cycle; and (c) imaging the mammal with an imager and obtaining an image of diseased cells with greater sensitivity compared with imaging in the absence of administration of the T-type calcium channel inhibitor.
2. The method of claim 1 , wherein the disease is a cancerous or pre-cancerous tumor.
3. The method of claim 1 , wherein the mammal is a human.
4. The method of claim 1 , wherein the T-type calcium channel inhibitor is selected from the group consisting of mibefradil, efonidipine, ethosuximide, TTL-1177, and nickel and combinations thereof.
5. The method of claim 1 , wherein the imaging marker is selected from the group consisting of 11 C-methionine, 2-deoxy-2-( 18 F)fluoro-D-glucose, and [ 18 F]-3′-fluoro-3′-deoxy-L-thymidine and combinations thereof.
6. The method of claim 5 , wherein the imaging marker is [ 18 F]-3′-fluoro-3′-deoxy-L-thymidine.
7. The method of claim 1 , wherein the T-type calcium channel inhibitor is administered for between about 1 and about 10 days, inclusively, prior to administering the imaging marker.
8. The method of claim 7 , wherein the T-type calcium channel inhibitor is administered for between about 5 and about 7 days, inclusively, prior to administering the imaging marker.
9. The method of claim 1 , wherein the administration of the T-type calcium channel inhibitor is stopped for about 30 minutes to about 72 hours prior to administration of the imaging marker.
10. The method of claim 1 , wherein the imager is selected from the group consisting of a magnetic resonance imager, a positron emission tomograph and a computer tomograph.
11. The method of claim 1 , wherein the T-type calcium channel inhibitor is administered to a concentration in a mammal's plasma of about 1 μM to about 10 μM.
12. The method of claim 1 , wherein T-type calcium channel inhibitor is mibefradil.
13. The method of claim 1 , wherein the disease is a cancer.
14. The method of claim 13 , wherein the disease is a cancerous tumor.
15. The method of claim 13 , wherein the T-type calcium channel inhibitor is mibefradil.
16. The method of claim 1 , wherein the disease is pre-cancerous.
17. The method of claim 1 , wherein the imaging marker is a positron emission tomography marker.
18. The method of claim 1 , wherein the imaging marker is 2-deoxy-2-( 18 F)fluoro-D-glucose.
19. The method of claim 1 , wherein the imager is a positron emission tomograph.
20. A method for increasing the sensitivity of imaging a cancer in a human which comprises the steps of:
(a) administering to the human an effective amount of mibefradil that inhibits proliferation of cancer cells by inhibiting cell cycle progression through the checkpoint between the G1 and S phase wherein the cancer cells accumulate at the G1/S checkpoint of the cell cycle;
(b) subsequently administering an imaging marker to the human after a period wherein cells that have accumulated at the G1/S checkpoint of the cell cycle following administration of the T-type calcium channel inhibitor have progressed to the S phase of the cell cycle, resulting in an increased proportion of the diseased cells in the S phase of the cell cycle; and
(c) imaging the human with an imager and obtaining an image of cancer cells with greater sensitivity compared with imaging in the absence of administration of the mibefradil.
21. The method according to claim 20 , wherein the imaging marker is 2-deoxy-2-( 18 F)fluoro-D-glucose and the imager is a positron emission tomograph.