Small molecule ligand for PSMA-targeted radioligand therapy
Prostate-specific membrane antigen (PSMA) is the most validated marker for prostate cancer. PSMA is overexpressed in nearly all prostate cancer cells, but its expression in normal prostate epithelium tissues and other normal tissues is 100-1000 fold lower. Therefore, PSMA has been widely used as a molecular receptor for various prostate cancer targeted therapies, such as radioligand therapy. Currently, DUPA (Mw 320 Da) is one of the most-widely investigated PSMA-specific ligands, and 177Lu-labeled DUPA is being evaluated in clinical trials as a PSMA-targeted radioligand therapy.
UMKC investigators have developed a small molecule ligand (Mw 349 Da) that binds to PSMA with very high specificity and high affinity (KD=0.7 nM). Its affinity to PSMA is approximately 30 times higher than that of DUPA (KD=21 nM). The newly discovered PSMA-specific ligand can provide a more effective approach for PSMA-targeted radioligand therapy or other PSMA-targeted drug delivery systems.