Synthesis of Radiolabeled Technetium- and Rhenium-Luteinizing Hormone-Releasing Hormone (99mTc/Re-Acdien-LHRH) Conjugates for Targeted Detection of Breast Cancer Cells Overexpressing the LHRH Receptor

Currently, 186/188 Re and 99m Tc are widely used radionuclides for cancer detection and diagnosis. New advancements in modalities and targeting strategies of radiopharmaceuticals will provide an opportunity to enhance imagery and detection of smaller colonies of cancer cells while lowering false-positive diagnoses. To understand the chemistry of agents derived from fac-[ 99m Tc(CO) 3 (H 2 O) 3 ] + species, the nonradioactive [Re(CO) 3 (H 2 O) 3 ] + analogue was used. We have designed and synthesized Re-Acdien-LHRH, Re-Acdien-peg-LHRH, and a radiolabeled 99m Tc-Acdien-LHRH (rhenium- and technetium-luteinizing hormone-releasing hormone) conjugates using a tridentate linker to detect cancers overexpressing the LHRH receptor. Re-Acdien-LHRH and Re-Acdien-peg-LHRH were synthesized from non-PEGylated and PEGylated LHRH-Acdien, respectively. Cellular uptake of the compounds 99m Tc-Acdien-LHRH, Re-Acdien-LHRH, and Re-Acdien-peg-LHRH was found to be significantly enhanced compared to that of untargeted 99m Tc alone and unlabeled [Re(CO) 3 (H 2 O) 3 ] + . In addition, the conjugate compounds showed no difference in cellular toxicity compared to untargeted 99m Tc alone or unlabeled [Re(CO) 3 (H 2 O) 3 ] + . Further, a competition assay using LHRH indicated selective targeting of Re-Acdien-peg-LHRH toward the LHRH receptor ( p < 0.05) compared to that of [Re(CO) 3 (H 2 O) 3 ] + alone. Together, our data show the design paradigm and synthesis of targeting radionuclides using the LHRH peptide. Our data suggests that utilizing the LHRH peptide can lead to selective targeting and diagnosis of breast cancers expressing the LHRH receptor.