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Contenido archivado el 2024-06-18

Oxygen Sensing with Multimodality Imaging Probes

Final Report Summary - O2SENSE (Oxygen Sensing with Multimodality Imaging Probes)

This project addresses the current unmet clinical need for new Imaging agents to supersede those currently used for imaging hypoxic tumours (in particular prostate cancer tumours) and which are not sensitive enough to the level of oxygen in vivo (pO2) to provide the desired level of selectivity for accurate diagnosis. Through O2SENSE we developed new
molecular imaging probes with increased responsiveness to hypoxic microenvironments, efficacy in multiple cancer types, and the capability to deliver simultaneous structural and functional information on cells and soft tissue. To achieve these objectives, we performed research at the interface between chemistry and biomedical research to: (a) develop ‘smart’ all-in-one multimodal imaging probes, whose sensitivities to pO2 in cells were tuneable to respond to various levels of hypoxia.
Thus, hypoxia sensitive imaging probes responsive to reduced levels of [O2] in living systems emerged as well as agents which are effective under anoxia. This aims to surpass the mainstay in cancer diagnosis and therapy and provides for increased selectivity for a wider range of tumours and we are focusing particularly on imaging and sensing for the early diagnosis of prostate tumours. The probes are suitable for interlocked Positron Emission Tomography (PET), Single Photon Emission Tomography (SPECT), and optical imaging methodologies including superresolution imaging and multiphoton fluorescence lifetime imaging techniques.

Our current programme has attracted industrial and clinical interest since it can help monitor the cellular bio localisation of the probes using multiphoton optical imaging in nearIR regimes. This, combined with in vitro and in vivo information from radioimaging techniques (PET, SPECT) will eventually provide an in depth understanding of biological processes and lead to the rational design of new diagnostics and therapeutics for personalised medicine. New chemical and spectroscopic tools developed together with our collaborators at the LSF CLF RAL, Research Complex at Harwell aimed to advance microscopy from the age of stains to that of molecular probes, which are able to provide real time imaging of physiological processes in cancer cells and tissues.

New highly responsive functional molecules and nanomaterials emerged from this programme, and show promise that they will become capable of operating at image resolutions ranging from nm to cm. These will drive the development of multi-photon imaging with sensitivity for various levels of hypoxia suitable for imaging in vivo. This work was highlighted in more than 24 new high profile publications since 2015 and several invited journal covers of international journals.