Decadentate Acyclic Chelators for Lanthanum Radiopharmaceuticals

Area of Science:

• Radiopharmaceutical Chemistry
• Coordination Chemistry
• Lanthanide Complexes

Background:

• Development of stable lanthanum complexes is crucial for radiopharmaceutical applications.
• Acyclic chelators with picolinic acid groups offer potential for high coordination numbers.

Purpose of the Study:

• To synthesize and characterize two novel acyclic chelators, H4TPAEN and H4TPADAC.
• To evaluate their complexation with La3+ for radiopharmaceutical development.
• To assess the stability and radiolabeling efficiency of the resulting complexes.

Main Methods:

• Synthesis of H4TPAEN and H4TPADAC chelators.
• X-ray crystallography and solution NMR for structural characterization of La3+ complexes.
• Determination of thermodynamic stability constants.
• Kinetics studies of complex dissociation.
• Radiolabeling with 135La and in vitro/in vivo stability assessments.

Main Results:

• Both chelators formed stable, ten-coordinated La3+ complexes with high thermodynamic stability constants (log KLaL = 19.16(8) for TPAEN4- and 19.55(1) for TPADAC4-).
• Quantitative radiolabeling with 135La was achieved efficiently at pH 4-5.
• The [135La]La3+-TPAEN4- complex exhibited significantly greater in vitro and in vivo stability compared to the [135La]La3+-TPADAC4- analogue.

Conclusions:

• H4TPAEN and H4TPADAC are effective chelators for La3+.
• The [135La]La3+-TPAEN complex shows excellent stability, particularly in vivo, indicating its potential for lanthanum-based radiopharmaceuticals.