18F—tagged inhibitors of prostate specific membrane antigen (PSMA) and their use as imaging agents for prostate cancer
The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers and imaging agents for various disease states of prostate cancer.
1. A compound of Formula I:
with:
i, j
0, 1
m
1-5
n
0-3
R
H, CH 3
AS
Natural or non-natural amino acid
Z:
—CO 2 H, —SO 2 H, —SO 3 H, —SO 4 H, —PO 2 H, —PO 3 H, —PO 4 H 2
X:
Naphthyl, Phenyl, Biphenyl, Indolyl (═2,3-benzopyrrolyl),
Benzothiazolyl, Quinoyl
Y:
Aryl, Alkylaryl, Cyclopentyl, Cyclohexyl, Cycloheptyl,
N-Piperidyl and N-methylated Piperidyl salt
18 F-Tag:
With:
x = 1-5
Carboydrate:
R 1 : Any alkyl, aryl or arylalkyl linker
especially methyl, 2-ethyl, 3-propyl,
2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, 2-,3-,4-phenylpropyl
R 2 : Any alkyl or aryl group
especially methyl isopropyl, tert-butyl,
phenyl or 1-naphtyl
R 1 : Any alkyl, aryl or arylalkyl linker
especially methyl, 2-ethyl, 3-propyl,
2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, 2-,3-,4-phenylpropyl
R 2 : Any alkyl or aryl group
especially methyl isopropyl, tert-butyl,
phenyl or 1-naphtyl
R 1 : Any alkyl, aryl or arylalkyl linker
especially methyl, 2-ethyl, 3-propyl,
2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, 2-,3-,4-phenylpropyl
R 2 : Any alkyl or aryl group
especially methyl isopropyl, tert-butyl,
phenyl or 1-naphtyl
R 1 : Any alkyl, aryl or arylalkyl linker
especially methyl, 2-ethyl, 3-propyl,
2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, 2-,3-,4-phenylpropyl
R 2 : Any alkyl or aryl group
especially methyl isopropyl, tert-butyl,
phenyl or 1-naphtyl
R 1 : Any alkyl, aryl or arylalkyl linker
especially methyl, 2-ethyl, 3-propyl,
2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, 2-,3-,4-phenylpropyl
R 2 : Any alkyl or aryl group
especially methyl isopropyl, tert-butyl,
phenyl or 1-naphtyl
R 1 : Any alkyl, aryl or arylalkyl linker
especially methyl, 2-ethyl, 3-propyl,
2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, 2-,3-,4-phenylpropyl
R 2 : Any alkyl or aryl group
especially methyl isopropyl, tert-butyl,
phenyl or 1-naphtyl
R 1 : Any alkyl, aryl or arylalkyl linker
especially methyl, 2-ethyl, 3-propyl,
2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, 2-,3-,4-phenylpropyl
R 2 : Any alkyl or aryl group
especially methyl isopropyl, tert-butyl,
phenyl or 1-naphtyl .
2. The compound of claim 1 , wherein the non-natural amino acid has the formula
and R′═H, CO 2 H, CH 2 CO 2 H, C 2 H 4 CO 2 H, CH(CO 2 H) 2 , CH(CH 2 CO 2 H) 2 , CH(CO 2 H)(CH 2 CO 2 H), CH 2 CH(CO 2 H) 2 , SO 3 H;
o=1-3; R═H, CH 3 .
3. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or ester thereof, and a pharmaceutically acceptable carrier.
4. The compound of claim 1 having the structure;
wherein the linker A is selected from the group consisting of:
wherein R 1 =(Glu)-(Urea)-(Lys) and R 2 =(Linker B) m - 18 F Tag, m=1-5,
and linker B is selected from the group consisting of:
5. The compound of claim 1 , selected from the following
6. The compound of claim 1 , wherein R 1 is selected from the group consisting of: methyl, 2-ethyl, 3-propyl, 2-,3-,4-phenyl, 2-,3-,4-phenylmethyl, and 2,3-,4-phenylpropyl.
7. The compound of claim 1 , wherein R 2 is selected from the group consisting of methyl, isopropyl, tert-butyl, phenyl, and 1-naphtyl.
8. A method of imaging a prostate region in a patient comprising the steps of:
(i) administering to a patient a diagnostically effective amount of the compound of claim 1 ;
(ii) exposing the prostate region of the patient to a scanning device to detect the 18F-tag; and
(iii) obtaining an image of the prostate region of the patient by the scanning device.