Small molecule targeted NIR dye conjugate for imaging LHRH receptor positive cancers

Overexpression of Luteinizing Hormone Releasing Hormone Receptor (LHRH-R) in various cancers and restricted expression of the receptor in healthy cells qualifies it as a valuable cancer biomarker. Previously, LHRH-R targeted peptides have been utilized to deliver attached payloads to LHRH-R expressing cancers. We report here for the first time the utilization of a small molecule non-peptidic ligand (BOEPL) of LHRH-R to deliver attached payloads to LHRH-R positive tumors. For this purpose, we linked the BOEPL ligand to a near infrared dye via various linkers. In vitro, these conjugates demonstrated low nanomolar binding affinity and in vivo they exhibited receptor-mediated uptake specifically in tumor tissue. Moreover, tumor uptake could be blocked by administration of excess unlabeled conjugate, and time course experiments showed retention of the dye conjugate in the tumor up to 12 h post injection. Because uptake of BOEPL-targeted NIR dye conjugates by nonmalignant organs/tissues was negligible and since the transient presence of targeted NIR dye in the kidneys was a result of clearance mechanism, we suggest that a BOEPL-targeted NIR dye might constitute a useful agent for fluorescence-guided surgery of LHRH-R positive cancers. Moreover, our results also provide proof of concept that BOEPL can be successfully used to deliver attached payloads to LHRH-R positive tumors in vivo.