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Imaging Chemistry and Biology (pre-2019)

Novel nanoscopic multimodal imaging agents and their applications – Optical, CT, PET/SPECT and MRI active nanoparticles

Project ID: 2016_206

Student: Megan Midson

1st supervisor: Mark Green, King’s College London
2nd supervisor: Nick Long, Imperial College London
3rd supervisor: Rafael T.M. de Rosales, King’s College London
4th supervisor: Phil Blower, King’s College London

The development of multimodal imaging agents is a key area of nanoparticle research. To have a single material that has the ability to image multiple disease states using one or more of several available techniques offers an obvious improvement in clinical applications. It also complements new developments in combined modality imaging instruments (e.g. PET/MR) leading to shorter waiting times and more accurate diagnosis.

Fig. 1   In vivo PET–MR imaging with [64Cu(dtcbp)2]– Endorem in a mouse. A,B) Coronal (top) and short axis (bottom) MR images of the lower abdominal area and upper hind legs showing the popliteal lymph nodes (solid arrows) before (A) and after (B) footpad injection of [64Cu(dtcbp)2]–Endorem. C) Coronal (top) and short-axis (bottom) NanoPET–CT images of the same mouse as in (B) showing the uptake of [64Cu(dtcbp)2]–Endorem in the popliteal (solid arrow) and iliac lymph nodes (hollow arrow). D) Whole-body NanoPET–CT images showing sole uptake of [64Cu(dtcbp)2]–Endorem in the popliteal and iliac lymph nodes. No translocation of radioactivity

In this multidisciplinary, cross-college project, we will prepare MFe2O4/BaYbF5;X,Y core/shell materials (M = Co, Mn; X, Y, =  Eu, Tm, Yb, Er, Ho, Tb) using organometallic chemistry developed in the research groups of Long and Green. We will then utilise a range of bisphosphonate ligands, developed by the Long/Torres groups to induce hydrophilicity whilst providing anchoring points for further radionuclides. In this manner, the ferrite core will provide MRI activity, the BaYbF5 shell will provide the CT functionality whilst the dopant rare-earth ions provide the optical emission. Numerous groups can be engineered into the ligands, including anchors for radionuclides (for PET/SPECT imaging) and further functional groups for the coordination of peptides, antibodies, etc.

The resulting multimodal particles will be evaluated preclinically in a wide range of imaging systems, including (i) initial cell tracking experiments using established mouse models in which conventional methods of cell tracking are established, jointly with the Blower group, (ii) mouse models of atherosclerotic plaque (collaboration with Botnar, KCL), (iii) pancreatic inflammation (collaboration with Peakman, KCL) and (iv) in breast cancer models (collaboration with Aboagye, ICL)

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