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Picolinamide-functionalized macrocyclic chelators for 203/212Pb theranostic radiotracers
Bradley E Osborne1,2, Christina Siakalli1,2, Ryan K Brown1
1Department of Chemistry, Imperial College London, Molecular Sciences Research Hub White City Campus London W12 0BZ UK n.long@imperial.ac.uk b.osborne18@imperial.ac.uk.
Inorganic Chemistry Frontiers
|June 22, 2026
Summary
Picolinamide-functionalized macrocycles show promise for lead-203/lead-212 theranostics. These ligands form stable complexes with lead, enabling potential advancements in targeted diagnostic imaging and radiotherapy.
Area of Science:
- Radiopharmaceutical Chemistry
- Nuclear Medicine
- Coordination Chemistry
Background:
- Picolinamide-functionalized macrocyclic ligands are explored for theranostic applications using lead-203/lead-212.
- These chelators offer potential for simultaneous diagnostic imaging and targeted radiotherapy.
Purpose of the Study:
- To synthesize and characterize novel picolinamide-functionalized diazacrown ligands (K22_PicAm and NPK_PicAm).
- To evaluate their complexation with non-radioactive Pb2+ and radiotherapeutic 212Pb2+.
- To assess their suitability for 203/212Pb-based theranostic agents.
Main Methods:
- Synthesis and structural characterization (NMR, X-ray diffraction) of ligands and Pb2+ complexes.
- Computational analysis (DFT, NBO) to understand electronic structure and geometry.
- Spectroscopic (UV-vis) and potentiometric titration studies for complex stability.
- Radiolabeling studies with 212Pb.
Main Results:
- Two 18-membered diazacrown ligands, K22_PicAm and NPK_PicAm, were successfully synthesized.
- Pb2+ complexes exhibited highly rigid, symmetric structures with holodirected geometries due to stereochemically inactive 6s2 lone pairs.
- Both ligands formed highly stable Pb2+ complexes, with complete binding observed between pH 4 and 9.
- Near-quantitative radiochemical conversion was achieved within 15 minutes using 212Pb.
Conclusions:
- Picolinamide-bearing macrocycles are effective chelators for lead radioisotopes.
- These ligands demonstrate significant potential for developing advanced 203/212Pb theranostic agents.
- Further research is warranted to explore their application in radiopharmaceutical development.
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