6-Alkoxymethyl-3-hydroxy-4H-pyranones: potential ligands for cell-labelling with indium

Area of Science:

• Radiochemistry
• Nuclear Medicine
• Bioconjugation Chemistry

Background:

• Cellular labeling with indium-111 (111In) is crucial for diagnostic imaging.
• Current ligands, such as tropolone, have limitations in efficiency and potential side effects.

Purpose of the Study:

• To identify and evaluate novel ligands for 111In-based cell labeling.
• To compare the efficacy and stability of new pyranone ligands against established tropolone.

Main Methods:

• Synthesis and characterization of novel 6-alkoxymethyl-3-hydroxy-4H-pyran-4-one ligands.
• Preparation of 111In complexes with the novel pyranone ligands and tropolone.
• Assessment of leukocyte labeling efficiencies and label stability in vitro.
• Evaluation of the inhibitory effects of ligands on metalloenzymes and platelet function.

Main Results:

• The novel pyranone ligands, 3-hydroxy-6-propoxymethyl-4H-pyran-4-one and 6-butoxymethyl-3-hydroxy-4H-pyran-4-one, demonstrated high labeling efficiencies for leukocytes.
• Labeling efficiencies of 111In complexes with pyranones were superior to those with 111In-tropolonate.
• Label stabilities were comparable between pyranone and tropolone complexes.
• 3-hydroxy-6-propoxymethyl-4H-pyran-4-one exhibited less inhibition of metalloenzymes and impairment of platelet function compared to tropolone.

Conclusions:

• 6-alkoxymethyl-3-hydroxy-4H-pyran-4-ones are effective ligands for 111In cell labeling, particularly for neutrophils and lymphocytes.
• These pyranone ligands offer potential advantages over tropolone due to higher labeling efficiency and reduced biological interference.
• The developed pyranones represent promising alternatives for radiopharmaceutical applications in nuclear medicine.