Synthesis and Preclinical Evaluation of 188Re-MAX-HEDP: A Promising Theranostics Strategy for Bone Metastases

Bone-associated disorders, including metastatic bone lesions, osteoporosis, and pathological fractures, require agents that can support both diagnostic imaging and targeted therapy. Theranostic radiopharmaceuticals provide an integrated approach for disease detection and radionuclide therapy.

This study aimed to design, synthesize, radiolabel, and evaluate a novel bone-targeting theranostic radiopharmaceutical, ¹⁸⁸Re-MAX-HEDP, for potential diagnostic and therapeutic applications for bone-related diseases.

A novel ligand, MAX-HEDP, was synthesized by conjugating hydroxyethylidene diphosphonic acid (HEDP) to the chelating moiety methoxy amido xanthate (MAX). The ligand was radiolabeled with rhenium-188 (¹⁸⁸Re). Labeling efficiency, chemical yield, in vitro stability under physiological conditions, and biodistribution in normal mice were evaluated.

The synthesis of MAX-HEDP achieved an overall chemical yield of 91%. Radiolabeling with ¹⁸⁸Re produced a highly stable complex, with a labeling efficiency exceeding 99%. Stability studies showed that more than 96% of the complex remained intact at ambient temperature, whereas degradation at 37 °C was less than 10%. Biodistribution studies demonstrated pronounced skeletal uptake of ¹⁸⁸Re-MAX-HEDP compared with uptake in other organs, confirming its strong bone-targeting potential.

¹⁸⁸Re-MAX-HEDP demonstrated a high synthesis yield, excellent radiolabeling efficiency, favorable stability, and selective skeletal accumulation. These findings suggest that it is a promising, cost-effective theranostic candidate for further clinical evaluation in the diagnosis and radionuclide therapy of bone malignancies and other bone-associated disorders.