Potential clinical applications of bimodal PET-MRI or SPECT-MRI agents

Abstract

The introduction to the clinic of positron emission tomography-magnetic resonance imaging scanners opens up the possibility to evaluate the real potential of bimodal imaging agents. In this mini-review, the limitations in the design and applications of these materials are summarised and the unique properties that may result in real clinical applications outlined.

Keywords: PET-MRI; SPECT-MRI; SPIO; medical imaging; multimodal agents.

scheme 1

Schematic representation of the two methods to use imaging agents for positron emission tomography-magnetic resonance imaging (PET-MRI) applications.

Figure 1

Bimodal agents for measuring the pH of tissues. (A) Gd-DOTA-4AMP-F developed by the group of Caravan et al. and (B) Gd-L developed by the group of Aime et al. In both cases, the positron emission tomography/single photon emission computed component is used to calculate the concentration of the contrast agent, making the pH measurement using the magnetic resonance imaging component possible.

Figure 2

Bimodal superparamagnetic iron oxides (SPIOs) for sentinel lymph node imaging. (A) Bifunctional bisphosphonates for single photon emission computed tomography and positron emission tomography imaging used for the radiolabelling of SPIOs; (B) Schematic representation of the radiolabelled dextran-coated SPIO (Endorem/Feridex). USPIO, ultra-small SPIO.

Figure 3

In vivo PET-MRI studies with ⁶⁴Cu(dtcbp)₂-Endorem in a mouse. (A) and (B): coronal (top) and short-axis (bottom) magnetic resonance 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 showing sole uptake of ⁶⁴Cu(dtcbp)₂-Endorem in the popliteal and iliac lymph nodes. No translocation of radioactivity to other tissues was detected. PET, positron emission tomography; MRI, magnetic resonance imaging; CT, computed tomography.

Figure 4

Positron emission tomography-magnetic resonance imaging (PET-MRI) of thrombi using bimodal agents. (A) EP-2104-R binds to fibrin fibres in thrombi and can be radiolabelled by partial exchange of Gd with the PET isotope ⁶⁴Cu. (B) After injection into an animal model, ⁶⁴Cu-EP-2104-R allows detection, localisation and quantification of the thrombi using PET-MRI with high sensitivity and spatial resolution. Arrows indicate the location of the thrombus. Image adapted with permission from the publisher of Reference .

Figure 5

Long circulating bimodal nanoparticles for PET-MR and SPECT-MRI. (A) Bisphosphonate anchors allow strong and stable binding of PEG polymers and radionuclides on the surface of the USPIOs; (B) The bimodal nanoparticles circulate in the bloodstream, as indicated by the strong imaging signal in the heart and vessels. The compound can be detected using radionuclide imaging and T1-MRI. Negligible uptake in the reticuloendothelial system was detected. PET, positron emission tomography; MRI, magnetic resonance imaging; USPIOs, ultra-small superparamagnetic iron oxide.