Project ID BE-MI2024_03


Co Supervisor 1A Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Department of Analytical, Environmental & Forensic SciencesWebsite

Co Supervisor 1B Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Department of Analytical, Environmental & Forensic SciencesWebsite

Imaging microbial infections via novel gallium-68 labelled aptamers

It has been estimated that more than 10 million deaths per year will occur by 2050 due to antimicrobial resistance (AMR). Therefore, there is an urgent need to develop novel infection-specific imaging techniques that can be translated into clinical practice as early diagnostic/prognostic agents.
This project aims to develop aptamer-based tracers as a novel infection-specific PET/CT in vivo imaging technique (Figure 1). DNA aptamers are short synthetic single-stranded DNA raised through systematic evolution of ligands by exponential enrichment (SELEX) process with a specific binding interaction to the target molecule(s) of choice. DNA aptamers have great benefits over other types of biological recognition moieties, including ease and cost-effective synthesis. Moreover, recent advances in DNA aptamers, including base modifications and chemical conjugation, allow improvements in binding specificities and in vivo aptamer stability without compromising target binding affinity. In recent years, gallium-68 based PET tracers have grown considerably because of their short half-life and commercial availability of 68Ge/68Ga generators for clinical usage. The developed microbial-specific aptamers will be chemically conjugated (via an appropriate linker) to a high-affinity gallium-68 chelators (developed at KCL), enabling the development of a novel microbial-specific imaging technique. The novel tracers will be tested in-vitro and – if time allows – in-vivo for microbial-specific uptake. Once developed, these imaging probes could potentially allow advanced non-invasive visualisation of infections and improve diagnostics in real patients, when studied as part of clinical studies. If successful, this microbial-specific imaging technique could be further employed to monitor the effectiveness of therapeutic treatments as well as potentially aid future antimicrobial stewardship strategies.
The student will acquire multidisciplinary skills spanning from synthetic/conjugation chemistries, radiochemistry, and microbiology and developing clinical research protocols.

Representative Publications

1. Gooch J, Tungsirisurp S, Costanzo H, Napier R, Frascione N*. Generating aptamers towards human sperm cells using massively parallel sequencing. Anal Bioanal Chem. 2021 Sep;413(23):5821-5834. doi: 10.1007/s00216-021-03562-7. Epub 2021 Aug 5. PMID: 34355252; PMCID: PMC8437879. 2. Developing aptasensors for forensic analysis Gooch, J., Daniel, B., Parkin, M. & Frascione, N.*, 1 Aug 2017, In: TRENDS IN ANALYTICAL CHEMISTRY. 94, p. 150-160 11 DOI: 10.1016/j.trac.2017.07.019; 3. DNA/RNA Aptamers for Illicit Drug Molecules Parkin, M. C. & Frascione, N., 2017, Detection of Drug Misuse: Biomarkers, Analytical Advances and Interpretation. Royal Society of Chemistry. 1. Young JD, Abbate V, Imberti C, Meszaros LK, Ma MT, Terry SYA, Hider RC, Mullen GE, Blower PJ. 68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling. J Nucl Med. 2017 Aug;58(8):1270-1277. doi: 10.2967/jnumed.117.191882. Epub 2017 Apr 13. PMID: 28408532; PMCID: PMC6175039. 2. Akter, A., Lyons, O., Mehra, V., Isenman, H. & Abbate, V.*, Radiometal Chelators for Infection Diagnostics; Front. Nucl. Med., 09 January 2023 Sec. Radionuclide Therapy Volume 2 – 2022 |; 3. Floresta, G., Keeling, G., Memdouh, S., Meszaros, L., T. M. de Rosales, R. & Abbate, V*.NHS-Functionalized THP Derivative for Efficient Synthesis of Kit-Based Precursors for 68Ga Labeled PET Probes; Apr 2021, In: Biomedicines. 9, 4, 367.