Macrocycle-Based Chelators for Room Temperature Chelation of Radioactive Isotopes

Background

The management of various cancers, particularly prostate cancer, increasingly relies on targeted radiotherapeutics and nuclear imaging for diagnosis and treatment monitoring. Current chelation methods often necessitate high temperatures, which can degrade thermally sensitive biomolecules, thereby limiting the range of potential targeting agents. Additionally, existing radiopharmaceutical constructs can also suffer from rapid systemic clearance, which reduces tumor accumulation and overall therapeutic efficacy. There is a continuous need for improved radiolabeling techniques that are compatible with diverse biomolecules and accessible to a wider range of clinical settings, alongside agents that exhibit prolonged circulation for enhanced tumor targeting and sustained therapeutic effect.

Technology

The Boros lab has developed Sc-18F ternary complexes that can form under mild, aqueous conditions, producing robust radiopharmaceuticals with a high radiochemical yield and specific activity. Corresponding in vivo imaging and biodistribution study with a cancer-targeting Sc-18F tracer indicates excellent in vivo stability and produces exquisite PET image quality, rendering the 18F/47Sc isotope pair an unusual, yet chemically sound theranostic pair with excellent potential to be put into clinical testing. This allows for a single dose of the drug to contain multiple dosages to allow the drug a sufficient amount of time to reach the cancer site and result in better PET or SPECT scans for treatment. Preclinical data already shows promising applications for prostate cancer using low dose radiotherapy. It is also able to identify picaga as a suitable chelator for therapeutic and diagnostic applications involving Lu-177.