Cell‐Surface labeling and internalization by a fluorescent inhibitor of prostate‐specific membrane antigen

Abstract

Our results suggest that potent, small-molecule inhibitors of PSMA can be utilized as carriers for targeted delivery for prostate cancer for future imaging and therapeutic applications.

99mTc-Labeled Small-Molecule Inhibitors of Prostate-Specific Membrane Antigen for Molecular Imaging of Prostate Cancer

“…This additional acid group did not negatively impact the affinity for PSMA. All 4 compounds exhibited high affinity and specificity for PSMA and internalized on binding to PSMA in LNCaP cells, as did previously described small molecules (14,40) and antibodies (10).…”

“…However, given the widespread availability of 99m Tc and the presence of SPECT cameras in most hospitals throughout the world, the development of a 99m Tc-labeled agent targeting a cell surface protein that is upregulated in prostate cancer may be advantageous. To improve prostate cancer detection for staging disease and to better monitor therapy and disease recurrence, we and others have attempted to image prostate cancer by targeting PSMA using small molecules (13)(14)(15)(18)(19)(20)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49) and antibodies that target the extracellular domain (41). Our previous work focused on using the glutamate-urea-lysine pharmacophore radiolabeled with an isotope of iodine that exhibited high affinity for PSMA and was found to localize to prostate cancer in animal models and in clinical trials (13)(14)(15).…”

Role of Prostate Specific Antigen (PSA) in Pathogenesis of Prostate Cancer

“…Some studies revealed that PSA inhibits the growth and migration of endothelial cells by inhibiting endothelial cell response to the fibroblast growth factor 2 (FGF-2) and vascular endothelial growth factor (VEGF). They have the ability cleave plasminogen, causing the release of biologically active angiostatin-like fragments and can essentially slow the progression of the disease through this antiangiogenic activity [32,60]; in addition to that, it has been revealed that PSA-inhibitors suppress the antiangiogenic effect of PSA in an angiogenesis model [61].…”

Detection of prostate-specific membrane antigen on HUVECs in response to breast tumor-conditioned medium

“…Recently, the successful deployment of PSMA inhibitors as targeting motifs for imaging and therapeutic agents suggests that such constructs can serve as pharmacokinetic alternatives to antibodies (25)(26)(27)(28)(29)(30). These studies also support the concept that such compounds may also be applied as diagnostic and therapeutic agents targeted to PSMA-positive (PSMA+) tumor-associated vasculatures of various non-prostatic tumors.…”