Labeled inhibitors of prostate specific membrane antigen (PSMA), biological evaluation, and use as imaging agents
The prostate-specific membrane antigen (PSMA) is increasingly recognized as a viable target for imaging and therapy of cancer. Various 99mTc/Re-labeled compounds were prepared by attaching known Tc/Re chelating agents to an amino-functionalized PSMA inhibitor with or without a variable length linker moiety. Ex vivo biodistribution and in vivo imaging demonstrated the degree of specific binding to engineered PSMA+ PC3 PIP tumors.
1. A compound of formula II:
Wherein
AA 1 is lysine and AA 2 is glutamic acid;
R′ is a substituted alkyl;
R″ is a substituted alkyl;
X and Z are each independently C 1 -C 8 alkylene, which may be substituted with 0-5 R A ;
W is C(═O);
Y is —NH—CO;
R A , for each occurrence, is CO 2 H.
2. The compound of claim 1 , wherein the compound is a compound of formula V:
wherein
R D is H;
each R E is H;
R 1 is pyridyl or quinolinyl;
R 2 is pyridyl, quinolinyl or —COOH;
R A , for each occurrence, is CO 2 H;
m is 1; and
each n is independently 1-8;
and each q is independently 0 or 1.
3. The compound of claim 2 , selected from the following:
4. The compound of claim 1 further comprising a metal, of formula IX:
wherein
M is 99m-Tc or Re;
AA 1 is lysine and AA 2 is glutamic acid;
R L is CO;
R′ is a substituted alkyl;
R″ is a substituted alkyl;
X and Z are each independently C 1 -C 8 alkylene, each of which may be substituted with 0-5 R A ;
Y is —NH—CO— and W is —C(═O)—;
R A , for each occurrence, is CO 2 H; and
r is 1-5.