Synthesis of Methoxy Amido Xanthate Ligand and Preliminary Rhenium-188 Radiolabeling Studies.

BACKGROUND

Rhenium-188 (188Re) is a high-energy β--emitting radionuclide with favorable physical and chemical properties for targeted radionuclide therapy and theranostic applications. In this study, a novel sulfur- and nitrogen-containing chelator, methoxy amido xanthate (MAX), was synthesized and evaluated for efficient radiolabeling with 188Re. In a second step, radiolabeling of the alendronate bisphosphonate was assessed for potential theranostic applications in bone metastases.

OBJECTIVES

This study aimed to synthesize and characterize the MAX ligand, optimize its radiolabeling with 188Re, and evaluate the association between the 188Re-MAX complex and alendronate.

METHODS

The ligand was prepared by reacting chloroacetamide with xanthate derivatives and was characterized using Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. Radiolabeling was performed using generator-eluted sodium perrhenate (188ReO4 -) under reducing conditions using stannous chloride and ascorbic acid. Key parameters affecting labeling efficiency, including ligand concentration, pH, reducing agent amount, and the effect of ascorbic acid as a stabilizing agent, were systematically optimized. Radiochemical purity was assessed by instant thin-layer chromatography (ITLC). In the second step, varying amounts of alendronate were added to 188Re-MAX under optimal conditions at 100°C for 30 minutes, and radiochemical purity was measured to determine the optimal alendronate amount.

RESULTS

Under optimal conditions (pH 5 - 6), radiochemical yields exceeding 98% were achieved at 100°C (80 - 100 mCi of 188Re, 12 mg MAX, 6 mg SnCl2, and 4 mg ascorbic acid) for 188Re-MAX. These findings indicate that the MAX ligand forms a stable complex with 188Re and represents a promising platform for the development of therapeutic and theranostic radiopharmaceuticals. For 188Re-MAX-alendronate, 96% radiochemical purity was achieved by adding 8 mg of alendronate to the mixture at pH 5 - 6.

CONCLUSIONS

A novel MAX ligand was successfully synthesized and radiolabeled with 188Re under mild conditions. Alendronate was also labeled using 188Re-MAX. High radiochemical yields and purity were achieved by optimizing key labeling parameters. Given the favorable physical characteristics of 188Re and the strong chelation observed, the 188Re-MAX complex is a viable candidate for the development of therapeutic and theranostic radiopharmaceuticals. The 188Re-MAX complex demonstrated favorable radiochemical properties and warrants further biological evaluation, including toxicity, stability, biodistribution, and dosimetric studies, before therapeutic application can be considered.