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

[Image: see text] 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.