Cancer specific radiolabeled conjugates regulated by the cell cycle for the treatment and diagnosis of cancer
View Patent ↗Radiolabeled conjugates are disclosed which have a component that is effective to target tumor cells, which cells selectively take up and degrade the conjugate, thereby delivering to the tumor cell nucleus a radioisotope capable of being incorporated into the nuclear material, so as to produce a cytotoxic effect and/or to render the cell detectable by radioimaging.
1. A cancer-specific radiolabeled conjugate of the formula:
wherein B* represents uracil substituted with a radionuclide; R represents H, OH, or O-L-DHT, L being a cleavable bifunctional linking moiety and DHT is 4-dihydrotestosterone which is bound through its hydroxyl substituent to said linking moiety; and R′ represents H or a group having the formula—PO(OR a )(OR b ), —PO(OR a )(ODHT) or —PO(ODHT) 2 , R a and R b being the same or different and representing H or lower alkyl having 1–8 carbon atoms and DHT is as previously defined, with the proviso that at least one of the R and R′ substituents comprises a DHT moiety.
2. The conjugate of claim 1 , wherein said radionuclide is an Auger electron-emitting radioisotope selected from the group of 123 I, 125 I, 77 Br, 80m Br, 195m Hg and 113 Sn.
3. The conjugate of claim 1 , wherein said radionuclide is selected from the group of 131 I, 32 P, and 225 At.
4. The conjugate of claim 1 , wherein said radionuclide is 125 I.
5. The conjugate of claim 1 , having the formula:
6. The conjugate of claim 1 having the formula:
7. The conjugate of claim 1 having the formula:
8. The conjugate of claim 1 having the formula;
9. The conjugate of claim 1 having the formula:
10. A method of treatment of a malignant tumor in a patient in need of such treatment, said tumor comprising cells having androgen receptor, said method comprising administering a therapeutically effective amount of the radiolabeled conjugate of claim 1 .
11. The method of claim 10 , wherein said cells are prostate cancer cells.
12. The method of claim 10 , wherein said cells are ovarian cancer cells.
13. The method of claim 10 , wherein said cells are breast cancer cells.
14. The method of claim 10 , wherein said radiolabeled conjugate is administered by a method selected from the group consisting of intravenously, intraperitoneally, and intratumor.
15. The method of claim 14 , wherein said method of administration is administered intravenously.
16. The method of claim 14 , wherein said conjugate is administered periodically for a term of years.
17. The method of claim 16 , wherein said conjugate is administered daily.
18. A method for the diagnosis of a malignant tumor in a patient, said tumor comprising cells having androgen receptor, said method comprising administering an effective amount of a radiolabeled conjugate of claim 1 , and then imaging the tumor scintigraphically.