Long-chain rhenium and technetium glucosamine conjugates

Area of Science:

• Organometallic Chemistry
• Radiopharmaceutical Chemistry
• Bioconjugation

Background:

• Development of targeted radiopharmaceuticals requires novel chelating agents.
• Glucosamine conjugation offers potential for targeted delivery.
• Technetium-99m and Rhenium offer unique radiolabeling properties.

Purpose of the Study:

• To synthesize and characterize novel glucosamine-conjugated organometallic complexes of technetium-99m and rhenium.
• To evaluate the potential of these complexes as enzyme substrates/inhibitors.
• To assess the cytotoxicity and cellular uptake mechanisms of the synthesized complexes.

Main Methods:

• Synthesis of glucosamine-conjugated ligands with pyridyl-tert-nitrogen-phenol or cyclopentadienyl groups.
• Complexation with [Re(CO)3(H2O)3]Br and [(99m)Tc(CO)3(H2O)](+).
• Radiolabeling yield determination, stability assays, hexokinase inhibition assays, MTT cytotoxicity tests, and GLUT-1 mediated cell uptake studies.

Main Results:

• Successful synthesis of five glucosamine-conjugated organometallic complexes.
• High radiolabeling yields (87–93%) and stability for technetium-99m complexes.
• Two rhenium complexes demonstrated competence as hexokinase inhibitors.
• Complexes showed no significant cytotoxicity at tested concentrations.
• Cellular uptake of technetium-99m complexes correlated with lipophilicity, indicating passive diffusion.

Conclusions:

• Novel glucosamine-conjugated technetium-99m and rhenium complexes were synthesized.
• The complexes exhibit promising characteristics for potential pharmaceutical applications, including enzyme inhibition.
• Cellular uptake is primarily driven by lipophilicity, suggesting passive diffusion rather than GLUT-1 mediation.