Cellular distribution by 2-photon fluorescence of complexes of metallic radioisotopes for imaging and therapy

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry

Abstract

Diagnostic medical imaging using radioactive isotopes (PET or SPECT imaging) is an important tool for clinicians to be able to assess patients both before and after treatment and thence to monitor progress. Many of the compounds used contain radioactive metals such as technetium, copper and indium. Detection of the radiation emitted from a patient following injection of the radioactive compound gives images with a resolution of 1-2mm which show for instance the location of a tumour. However once inside the body the radioactive compounds are taken up in cells and this can determine how effectively an imaging agent targets a disease site. PET and SPECT imaging cannot be used to uncover what happens within cells as these are much smaller than the resolution limit of 1-2mm. Some compounds will emit ultraviolet or visible radiation following excitation with radiation at a different wavelength; a phenomenon known as fluorescence. This has much higher resolution than PET or SPECT and we propose to use this technique to reveal how potential metal based PET and SPECT imaging agents are behaving within living cells. This requires the design of compounds that not only target specific disease sites but are also fluorescent. The information from fluorescence will give invaluable information about the mechanisms by which the compounds are trapped at the target disease sites and this can be then be used to redesign the compound to improve its imaging performance. Diagnostic imaging is now a key part of modern medicine and improved PET and SPECT agents would make a significant contribution to obtaining more accurate diagnosis for patients and enabling the treatment to be tailored to an individual patients needs. This concept of personalised medicine is seen worldwide as a major goal for the future.

Technical Summary

The project involves the application of 2-P fluorescence confocal microscopy and lifetime emission measurements to determine details of the mechanism of action at the cellular level of fluorescent metallic complexes with potential applications as PET or SPECT imaging or therapeutic agents. A major focus is Cu and related complexes for imaging hypoxia, but potential cancer therapeutic agents and other imaging targets are also addressed

Publications

10 25 50
 
Description ERC Advanced Researcher Award
Amount £1,600,000 (GBP)
Organisation European Research Council (ERC) 
Sector Public
Country European Union (EU)
Start 03/2011 
End 03/2016
 
Title Ratiometric Oxygen Probe 
Description This is a lanthanide based material that responds to the presence of oxygen through changes in the colour of the luminecence, allowing for ratiometric imaging 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact Having demonstrated concept, we are currently developing the probe further, and testing uptake into cells.A UK patent application was filed in May 2014 
 
Description Fluorescence Imaging of oxygen concentration 
Organisation King's College London
Department School of Medicine KCL
Country United Kingdom 
Sector Academic/University 
PI Contribution The group have developed a new system for ratiometric luminescence imaging of oxygen concentrations inside cells that combines a signal channel with a reference channel that allows concentration of the probe to be monitored. Second generation systems that enhance performance are currently being developed
Collaborator Contribution LSF are developing new methods for intracellular imaging that will permit us to study NIR luminescence inside cells in water absorption windows. Invesitgation of cell uptake mechannisms of luminescent probesEnd users
Impact IP protection and publication are in progress. The collaboration involves clinical and non-clinical scientists, and spans chemistry, physics and biomedical sciences.
Start Year 2011
 
Description Fluorescence Imaging of oxygen concentration 
Organisation Rutherford Appleton Laboratory
Country United Kingdom 
Sector Public 
PI Contribution The group have developed a new system for ratiometric luminescence imaging of oxygen concentrations inside cells that combines a signal channel with a reference channel that allows concentration of the probe to be monitored. Second generation systems that enhance performance are currently being developed
Collaborator Contribution LSF are developing new methods for intracellular imaging that will permit us to study NIR luminescence inside cells in water absorption windows. Invesitgation of cell uptake mechannisms of luminescent probesEnd users
Impact IP protection and publication are in progress. The collaboration involves clinical and non-clinical scientists, and spans chemistry, physics and biomedical sciences.
Start Year 2011
 
Description Fluorescence Imaging of oxygen concentration 
Organisation University of Bath
Department Department of Chemistry
Country United Kingdom 
Sector Academic/University 
PI Contribution The group have developed a new system for ratiometric luminescence imaging of oxygen concentrations inside cells that combines a signal channel with a reference channel that allows concentration of the probe to be monitored. Second generation systems that enhance performance are currently being developed
Collaborator Contribution LSF are developing new methods for intracellular imaging that will permit us to study NIR luminescence inside cells in water absorption windows. Invesitgation of cell uptake mechannisms of luminescent probesEnd users
Impact IP protection and publication are in progress. The collaboration involves clinical and non-clinical scientists, and spans chemistry, physics and biomedical sciences.
Start Year 2011
 
Description Demonstration Lecture, Science Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact About fifty children attended a demonstration lecture and subsequent question and answer session showing how luminescence could be used to distinguish between species in solution.

Frther requests for outreach work have been received, and local schools are seeking Royal Society funding for a "forensic" chemistry roadshow.
Year(s) Of Engagement Activity 2010