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

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.

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.

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.

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.

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.