Project ID BE-MI2023_01

ThemeBE-MI

Co Supervisor 1A AEFS, IPSWebsite

Co Supervisor 1B AEFS, IPSWebsite

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 the 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 pose 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.

Figure 1: schematic approach of aptamer-based microbial PET imaging.

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 in future antimicrobial stewardship strategies.

The student will acquire multidisciplinary skills spanning from synthetic/conjugation chemistries, radiochemistry, and microbiology and developing clinical research protocols.

One representative publication from each co-supervisor:

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.

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.