18F-tagged inhibitors of prostate specific membrane antigen (PSMA), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer
The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of prostate cancer.
1. A compound of formula (la) or (lb):
with:
n is 0 or 1;
m is 0, 1, 2, 3 or 4, with the proviso that m + n > 0;
Z is —CO 2 H, —SO 2 H, —SO 3 H, —SO 4 H, —PO 2 H, or —PO 4 H 2 ;
X is naphthyl, phenyl, biphenyl, indolyl (=2,3-benzopyrrolyl),
or benzothiazolyl;
Y is aryl, alkylaryl, cyclopentyl, cyclohexyl, or cycloheptyl; and
18 F-Tag is
With:
x = 1-5
wherein the carbohydrate is
With:
x = 1-5
wherein the carbohydrate is
R 1 : Any alkyl, aryl or arylalkyl linker and
R 2 : Any alkyl or aryl group;
R 1 : Any alkyl, aryl or arylalkyl linker and
R 2 : Any alkyl or aryl group;
R 1 : Any alkyl, aryl or arylalkyl linker and
R 2 : Any alkyl or aryl group;
R 1 : Any alkyl, aryl or arylalkyl linker and
R 2 : Any alkyl or aryl group;
R 1 : Any alkyl, aryl or arylalkyl linker and
R 2 : Any alkyl or aryl group;
R 1 : Any alkyl, aryl or arylalkyl linker and
R 2 : Any alkyl or aryl group; or
R 1 : Any alkyl, aryl or arylalkyl linker and
R 2 : Any alkyl or aryl group.
2. The compound of claim 1 having the structure R′-Linker-R with R′= 18 F-Tag and R=Glu-Urea-Lys:
wherein the linker is
3. The compound of claim 1 ,
wherein the 18 F-Tag is
and R 1 is a methyl, 2-ethyl, 3-propyl, 2-,3-,4-phenyl, 2-, 3-,4-phenylmethyl, or 2-,3-,4-phenylpropyl linker.
4. The compound of claim 1 ,
wherein the 18 F-Tag is
and R 2 is methyl, isopropyl, tert-butyl, phenyl or 1-naphtyl.
5. The compound of claim 1 ,
wherein the 18 F-Tag is
R 1 is a methyl, 2-ethyl, 3-propyl, 2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, or 2-,3-,4-phenylpropyl linker and
R 2 is methyl, isopropyl, tert-butyl, phenyl or 1-naphtyl.
6. The compound of claim 1 , wherein the compound is:
7. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt, or ester thereof, and a pharmaceutically acceptable carrier.
8. A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt, or ester thereof, and a pharmaceutically acceptable carrier.
9. A pharmaceutical composition comprising the compound of claim 6 , or a pharmaceutically acceptable salt, or ester thereof, and a pharmaceutically acceptable carrier.
10. A method of imaging in a patient comprising administering the compound of claim 1 to the patient.
11. A method of diagnosing prostate cancer and/or metastasis thereof comprising administering the compound of claim 1 .
12. A method of treating prostate cancer and/or metastasis thereof comprising administering the compound of claim 1 .
13. A method of imaging in a patient comprising administering the compound of claim 2 to the patient.
14. A method of diagnosing prostate cancer and/or metastasis thereof comprising administering the compound of claim 2 .
15. A method of treating prostate cancer and/or metastasis thereof comprising administering the compound of claim 2 .
16. A method of imaging in a patient comprising administering the compound of claim 6 to the patient.
17. A method of diagnosing prostate cancer and/or metastasis thereof comprising administering the compound of claim 6 .
18. A method of treating prostate cancer and/or metastasis thereof comprising administering the compound of claim 6 .