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Flexible Peptide Decorated Polyaminocarboxylate Ligands for Selective Extraction of Radiotherapeutic Metals for Targeted Alpha Cancer Therapy


   Department of Chemistry

  , ,  Applications accepted all year round  Funded PhD Project (UK Students Only)

About the Project

Nuclear fission produces radioactive isotopes with decay products encompassing a large proportion of the Periodic Table. Many of these isotopes are considered as waste and are currently disposed of following separation. However, a number of medically useful therapeutic radioisotopes are contained within this waste stream and remain an untapped resource; specifically, alpha therapeutic agents such as Ac-225 and Pb-212 (originating from uranium and thorium) which may be used for cancer treatment. Reactor produced radionuclides require rapid and selective separation in a few simple steps before they can undergo bioconjugation to a suitable targeting vector to make them viable as cancer therapeutics. However, the coordination chemistry of these radionuclides differs and achieving direct selective extraction remains challenging. 

This project will build on preliminary work developed in the group to develop radiation resistant selective extractants for therapeutic radionuclides currently disposed of in reactor waste streams. The extractants are peptide appended polyaminocarboxylate chelators with variable backbone length and donor atoms. The donor atoms and the amino acid/peptide sequence and the extracted species will be fully characterised using standard analytical techniques. Once a given metal ion is extracted, (aqueous to organic phase or vice versa depending on the target radionuclide), the peptide appendages can be rapidly bioconjugated to a known protein/targeting vector using established chemistry and their suitability for cancer therapy assessed in vitro using fluorescence spectroscopy and microscopy in suitable cell cultures. This project is 50% funded by the National Nuclear Laboratory (NNL) through its Health and Nuclear Medicine Core Science Theme, and as such it is envisaged that the student would undertake a research placement within NNL’s laboratories during the project.

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References

https://www.nnl.co.uk/
K. Yong and M. Brechbiel, AIMS Medical Science, 2015, 2, (3), 228. DOI:10.3934/medsci.2015.3.228.
McNeil et al. EJNMMI Radiopharmacy and Chemistry, 2021 6, 6. DOI:10.1186/s41181-021-00121-4.

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