Multimodal liposomes for SPECT/MR imaging as a tool for in situ relaxivity measurements

One of the major challenges of MR imaging is the quantification of local concentrations of contrast agents. Cellular uptake strongly influences different parameters such as the water exchange rate and the pool of water protons, and results in alteration of the contrast agent's relaxivity, therefore making it difficult to determine contrast agent concentrations based on the MR signal only. Here, we propose a multimodal radiolabeled paramagnetic liposomal contrast agent that allows simultaneous imaging with SPECT and MRI. As SPECT-based quantification allows determination of the gadolinium concentration, the MRI signal can be deconvoluted to get an understanding of the cellular location of the contrast agent. The cell experiments indicated a reduction of the relaxivity from 2.7 ± 0.1 m m(-1)  s(-1) to a net relaxivity of 1.7 ± 0.3 m m(-1)  s(-1) upon cellular uptake for RGD targeted liposomes by means of the contrast agent concentration as determined by SPECT. This is not observed for nontargeted liposomes that serve as controls. We show that receptor targeted liposomes in comparison to nontargeted liposomes are taken up into cells faster and into subcellular structures of different sizes. We suggest that the presented multimodal contrast agent provides a functional readout of its response to the biological environment and is furthermore applicable in in vivo measurements. As this approach can be extended to several MRI-based contrast mechanisms, we foresee a broader use of multimodal SPECT/MRI nanoparticles to serve as in vivo sensors in biological or medical research.