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Developing a Pipeline for Reliable, Agile Production of Radiopharmaceuticals: (EPSRC DTP)


Project Description

This project consists of three components (1) Development of a transmutation/radiopharmacy synthesis platform at the Dalton Cumbrian Facility (DCF); (2) Synthesis of clinically relevant radionuclides, 64Cu,72As and 89Zr as exemplars for the development of a medical radiopharmaceutical production facility; (3) Formulating novel therapeutic and diagnostic compounds including radionuclide therapeutic nanoparticles based on EGFR-targeted 64Cu/Au amalgams.

Radionuclides, produced in nuclear reactors or by beamline irradiation, are essential components of medical imaging and treatment strategies. The utilisation of radionuclides is increasing due to their potential to deliver personalised medicine in cancer imaging and treatment using radiolabelled antibodies or small protein/peptide molecules targeting cell surface molecules specific to cancer subtypes such as EGFR. Imaging using positron emission tomography is the most sensitive technique for the detection of primary tumours and secondary spread.

Currently most therapeutic radionuclides and the radioactive metals used to label peptide and small proteins are imported, but could be manufactured in the UK or alternatives could be produced with similar nuclear properties. The first component of the project will involve the student optimising the fabrication of 47Sc (useful as a therapeutic), 64Cu (versatile for both PET imaging and therapy) and 89Zr (excellent for PET imaging) at DCF. DCF’s beam currents are significantly higher than those available elsewhere; meaning transmutations can be performed faster and with greater yields. However, samples need rapid cooling, which will be achieved by developing a moving target. Additionally, we will draw on our radiation sample handling experience to couple this target to an automated sample-handling system able to extract and purify the transmuted isotopes and then feed them into chemical synthesis processes.

Low energy β-emitters are effective for treating small tumours but large primary or secondary tumours are more effectively treated using higher energy β-emitters [1,2]. Metastatic cancer is characterised by multiple malignant lesions of sizes varying from <1mm to, in some cases > 10cm. Therapeutics consisting of radionuclides combining low and medium/high β-energies would be more universally utilisable. Alloying/plating 64Cu in gold (a rapid process) spiked with 198Au (medium energy β with a tissue penetration maximum of about 5 mm) and targeted with anti-EGFR-antibodies will be explored and pre-clinically examined. Radiation transport modelling will be used to inform the preclinical results – our team leads the development of an award-winning software training package ideal for these calculations so the student concerned will have access to the latest training materials for this component of the project [3].

Entry Requirements:

Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

On the online application form select PhD Cell Biology. For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/)




Funding Notes

EPSRC DTP studentship with funding for a duration of 3.5 years to commence in September 2020. The studentship covers UK/EU tuition fees and an annual minimum stipend £15,285 per annum. Due to funding restrictions, the studentship is open to UK and EU nationals with 3 years residency in the UK.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

Lee St, Burvenich I, Scott AM. Noel target selection for nuclear medicine studies Sem. Nucl. Med. 2019; 49:357-368

Langbein T, Weber WA Eiber M. Future of Theranostics: An outlook on precision oncology in nuclear medicine. J. Nucl. Med. 2019; 30: 13S-19S.

Perl, J; Villagomez-Bernabe, B; Currell, F TOPAS_edu: A Window Into the Stochastic World Through the TOPAS Tool for Particle Simulation Medical Physics 2105; 42 3557-3557 and winner of Innovation in Education of the Year award at the 2015 American Association of Physics in Medicine annual meeting

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