An efficient chelator for complexation of thorium-227

Area of Science:

• Radiochemistry
• Medicinal Chemistry
• Oncology

Background:

• Thorium isotopes are investigated for targeted cancer therapy.
• Development of efficient chelators is crucial for stable radiometal complexation.
• Hydroxypyridinone compounds are known for their metal-binding properties.

Purpose of the Study:

• To synthesize and characterize a novel octadentate hydroxypyridinone-based thorium chelator.
• To evaluate the stability and formation kinetics of thorium complexes.
• To assess the in vivo biodistribution of the chelator for potential therapeutic applications.

Main Methods:

• Synthesis of an octadentate hydroxypyridinone derivative.
• Complexation studies with Th-227.
• In vivo biodistribution studies in mice.

Main Results:

• The synthesized chelator forms highly stable Th-227 complexes rapidly at ambient temperature.
• Mouse biodistribution showed rapid hepatobiliary excretion and low bone uptake, indicating in vivo complex stability.
• The chelator possesses an activatable carboxylic acid group for bioconjugation.

Conclusions:

• This novel thorium chelator exhibits excellent properties for targeted radiopharmaceutical development.
• The chelator is suitable for creating Targeted Thorium Conjugates (TTCs) for oncology.
• Its rapid complexation, stability, and favorable excretion profile make it a promising candidate for further investigation.