Cyanine-containing compounds for cancer imaging and treatment
This invention relates generally to cyanine-containing compounds; pharmaceutical compositions comprising cyanine-containing compounds; and methods of using cyanine-containing compounds for cancer cell imaging, cancer cell growth inhibition, and detecting cancer cells, for example. Compounds of the invention are preferentially taken up by cancer cells as compared to normal cells. This allows many uses in the cancer treatment, diagnosis, tracking and imaging fields.
1. A method of imaging cancer cells, wherein the method comprises introducing to the cancer cells an imaging amount of a compound of the formula shown below
wherein each of R 5 is H; and
wherein the R substituents are the same, or are not the same; and
wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 3 COOH, or an ester or amide thereof, (CH 2 ) 4 COOH, or an ester or amide thereof, (CH 2 ) 5 COOH, or an ester or amide thereof, (CH 2 ) 6 COOH, or an ester or amide thereof, (CH 2 ) 7 COOH, or an ester or amide thereof, (CH 2 ) 8 COOH, or an ester or amide thereof, (CH 2 ) 9 COOH, or an ester or amide thereof, (CH 2 ) 3 SO 3 H, (CH 2 ) 4 SO 3 H, (CH 2 ) 5 SO 3 H, (CH 2 ) 6 SO 3 H, (CH 2 ) 7 SO 3 H, (CH 2 ) 8 SO 3 H, and CH 2 ) 9 SO 3 H;
exposing the cancer cells to electromagnetic radiation; and
detecting light emission from the compound; and
wherein the compound is introduced to one or more cancer cells without a targeting agent; and
wherein the amide of the R substituent is not tagged with a radioactive group; and
wherein if the compound is used in combination with a therapeutic agent or radioactive agent, the agent is co-administered with the compound simultaneously or sequentially, and is not linked to the compound.
2. The method of claim 1 , wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 3 COOH, (CH 2 ) 4 COOH, (CH 2 ) 5 COOH, (CH 2 ) 6 COOH, (CH 2 ) 7 COOH, (CH 2 ) 8 COOH, (CH 2 ) 9 COOH, (CH 2 ) 3 SO 3 H, (CH 2 ) 4 SO 3 H, (CH 2 ) 5 SO 3 H, (CH 2 ) 6 SO 3 H, (CH 2 ) 7 SO 3 H, (CH 2 ) 8 SO 3 H, and (CH 2 ) 9 SO 3 H.
3. The method of claim 1 , wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 5 COOH, or an ester or amide thereof, (CH 2 ) 4 COOH, or an ester or amide thereof, (CH 2 ) 3 COOH, or an ester or amide thereof, and (CH 2 ) 4 SO 3 H.
4. The method of claim 1 , wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 5 COOH, (CH 2 ) 4 COOH, (CH 2 ) 3 COOH, and (CH 2 ) 4 SO 3 H.
5. The method of claim 1 , wherein the R substituents are selected from two acid groups, one acid and one ester group, and two ester groups.
6. The method of claim 1 , wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 5 COOH, and (CH 2 ) 4 SO 3 H.
7. A method of claim 1 , wherein the method comprises introducing to the cancer cells an imaging amount of a compound selected from the group consisting of: MHI-148, MHI-25 (also known as IR783), MHI-160, and MHI-161, an ester of each thereof, or an amide of each thereof.
8. The method of claim 1 , wherein the method comprises introducing to the cancer cells an imaging amount of MHI-25 (also known as IR783), or an ester or amide thereof.
9. The method of claim 1 , wherein the cancer cells are imaged in vivo.
10. The method of claim 1 , wherein the cancer cells comprise lymphoma, myeloid leukemia, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, ovarian cancer, cervical cancer, bone cancer, thyroid cancer, adrenal gland cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, skin cancer, liver cancer, testicular cancer, colon cancer, or breast cancer cells.
11. A method of treating cancer, the method comprising administering to a patient in need thereof a therapeutically effective amount of a compound of the formula shown below
wherein each of R 5 is H; and
wherein the R substituents are the same, or are not the same; and
wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 3 COOH, or an ester or amide thereof, (CH 2 ) 4 COOH, or an ester or amide thereof, (CH 2 ) 5 COOH, or an ester or amide thereof, (CH 2 ) 6 COOH, or an ester or amide thereof, (CH 2 ) 7 COOH, or an ester or amide thereof, (CH 2 ) 8 COOH, or an ester or amide thereof, (CH 2 ) 9 COOH, or an ester or amide thereof, (CH 2 ) 3 SO 3 H, (CH 2 ) 4 SO 3 H, (CH 2 ) 5 SO 3 H, (CH 2 ) 6 SO 3 H, (CH 2 ) 7 SO 3 H, (CH 2 ) 8 SO 3 H, and CH 2 ) 9 SO 3 H; and
wherein the compound is introduced to one or more cancer cells of the patient without a targeting agent; and
wherein if the compound is used in combination with a therapeutic agent or radioactive agent, the agent is co-administered with the compound simultaneously or sequentially, and is not linked to the compound.
12. The method of claim 11 , wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 3 COOH, (CH 2 ) 4 COOH, (CH 2 ) 5 COOH, (CH 2 ) 6 COOH, (CH 2 ) 7 COOH, (CH 2 ) 8 COOH, (CH 2 ) 9 COOH, (CH 2 ) 3 SO 3 H, (CH 2 ) 4 SO 3 H, (CH 2 ) 5 SO 3 H, (CH 2 ) 6 SO 3 H, (CH 2 ) 7 SO 3 H, (CH 2 ) 8 SO 3 H, and CH 2 ) 9 SO 3 H.
13. The method of claim 11 , wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 5 COOH, or an ester or amide thereof, (CH 2 ) 4 COOH, or an ester or amide thereof, (CH 2 ) 3 COOH, or an ester or amide thereof, (CH 2 ) 2 COOH, or an ester or amide thereof, and (CH 2 ) 4 SO 3 H.
14. The method of claim 11 , wherein the R substituents are selected from wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 5 COOH, (CH 2 ) 4 COOH, (CH 2 ) 3 COOH, and (CH 2 ) 4 SO 3 H.
15. The method of claim 11 , wherein the R substituents are selected from two acid groups, one acid and one ester group, and two ester groups.
16. The method of claim 11 , wherein the R substituents are independently selected from the group consisting of: (CH 2 ) 5 COOH, and (CH 2 ) 4 SO 3 H.
17. The method of claim 11 , wherein the method comprises administering a therapeutically effective amount of a compound selected from the group consisting of: MHI-148, MHI-25 (also known as IR783), MHI-160, MHI-161, an ester of each thereof, or an amide of each thereof.
18. The method of claim 11 , wherein the method comprises administering a therapeutically effective amount of MHI-25 (also known as IR783), or an ester or amide thereof.
19. The method of claim 11 , wherein the cancer cells are tracked during or after therapy by monitoring the accumulation of the compound in one or more cells or tissues of the patient by imaging.
20. The method of claim 11 , wherein the cancer cells comprise lymphoma, myeloid leukemia, bladder cancer, brain cancer, head and neck cancer, kidney cancer, lung cancer, myeloma, ovarian cancer, cervical cancer, bone cancer, thyroid cancer, adrenal gland cancer, cholangiocarcinoma, pancreatic cancer, prostate cancer, skin cancer, liver cancer, testicular cancer, colon cancer, or breast cancer cells.
21. The method of claim 1 , wherein an additional antineoplastic agent is used in the method, and the additional antineoplastic agent comprises a chemotherapeutic, radiation or biological response modifier.
22. The method of claim 11 , wherein an additional antineoplastic agent is used in the method, and the additional antineoplastic agent comprises a chemotherapeutic, radiation or biological response modifier.