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Smart Imaging Probes

18F-PSMA-bioharmonophore conjugates: a smart PET/optical tracer for improved prostate cancer detection and localisation 

Project ID: 2023_032

1st Supervisor: Dr Periklis (Laki) Pantazis, Imperial College London
2nd Supervisor: Dr Graeme Stasiuk , King’s College London
Clinical Supervisor: Prof Prokar Dasgupta, King’s College London

 

Aim of the PhD Project:

  • Generate 18F-PSMA-bioharmonophore peptide conjugates as smart imaging agents for prostate diagnosis.
  • Validate the PSMA-PET/nonlinear optics tracer in the detection and localisation of prostate cancer with human tumour tissue.

 

Lay Summary:

Context of research: Prostate cancer (PCa) is the second most common diagnosed tumour in males worldwide, with over one million new patients diagnosed every year. After PCa diagnosis, the precise determination of the extent of the lesion is a fundamental step for a tailor-made therapy. The earlier the detection and the more precise the diagnosis, the more effective the treatment and the longer the survival. Conventional imaging techniques like CT and MRI face significant limitations, as they cannot detect lesions measuring smaller than a few mm. The most recent nuclear medicine development is the use of prostate specific membrane antigen (PSMA) 18F-PET tracers that are emerging as the most promising tool of medical imaging, gaining ground every day. Yet 18F-PET scans must be interpreted carefully because noncancerous conditions can look like cancer, and some cancers do not appear on PET scans. To increase the predictive value of PET scans, i.e the likelihood that an individual with a positive or negative test result truly has or has not PCa, you will generate a smart diagnostic probe that links PSMA-18F-PET tracers to tripeptides that can self-assemble forming very bright and ultrastable optical imaging probes called bioharmonophores. Successful targeting of such a PET tracer conjugate to PCa cells will lead to their specific accumulation within cells. The proximity of these conjugates in vesicles will facilitate their self-assembly of the bioharmonophore tripeptides generating a high contrast, pH-resistant, non-toxic nonlinear signal with outstanding resolution and predictive value.

Potential applications and benefits:
The combination of PET imaging and cancer cell-inducible optical imaging of this smart imaging probe will dramatically improve the specificity and the predictive value when compared with conventional PET tracer imaging for (metastatic) prostate cancer. This conjugate will allow for more accurate diagnosis, staging and treatment follow-up in patients with PCa. As 18F-based PET tracers are readily available in most UK trusts, your PSMA-18F-PET tracer conjugate can be easily translated into the clinic.

Expected academic background of candidate:
The project will require a highly motivated student with a background in chemical engineering/medical physics who will be supervised by a truly interdisciplinary team: Dr Pantazis who invented bioharmonophores and is an expert in bioimaging and Dr Stasiuk who is an expert in PET imaging and preclinical prostate cancer.

 

References

  1. F. Brayet al.,CA Cancer J Clin 68, 394-424 (2018). 
  2. A. Ghosh, W. D. Heston,J Cell Biochem91, 528-539 (2004). 
  3. S. Fantiet al.,The Lancet Oncology 19, e696-e708 (2018). 
  4. A. Y. Sonayet al.,ACS Nano 10.1021/acsnano.0c10634 (2021). 
  5.  S. Y. Yap, et. al. , Chem. Commun., 56, 11090-11093 (2020). 
  6. G. Firth et al., Probe, Chem. Commun., , 54, 3227-3230 (2018) 

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