Multimodality imaging using SPECT/CT and MRI and ligand functionalized 99mTc-labeled magnetic microbubbles

Background: In the present study, we used multimodal imaging to investigate biodistribution in rats after intravenous administration of a new Tc-99m-labeled delivery system consisting of polymer-shelled microbubbles (MBs) functionalized with diethylenetriaminepentaacetic acid (DTPA), thiolated poly(methacrylic acid) (PMAA), chitosan, 1,4,7-triacyclononane-1,4,7-triacetic acid (NOTA), NOTA-super paramagnetic iron oxide nanoparticles (SPION), or DTPA-SPION. Methods: Examinations utilizing planar dynamic scintigraphy and hybrid imaging were performed using a commercially available single-photon emission computed tomography (SPECT)/computed tomography (CT) system. For SPION containing MBs, the biodistribution pattern of Tc-99m-labeled NOTA-SPION and DTPA-SPION MBs was investigated and co-registered using fusion SPECT/CT and magnetic resonance imaging (MRI). Moreover, to evaluate the biodistribution, organs were removed and radioactivity was measured and calculated as percentage of injected dose. Results: SPECT/CT and MRI showed that the distribution of Tc-99m-labeled ligand-functionalized MBs varied with the type of ligand as well as with the presence of SPION. The highest uptake was observed in the lungs 1 h post injection of Tc-99m-labeled DTPA and chitosan MBs, while a similar distribution to the lungs and the liver was seen after the administration of PMAA MBs. The highest counts of Tc-99m-labeled NOTA-SPION and DTPA-SPION MBs were observed in the lungs, liver, and kidneys 1 h post injection. The highest counts were observed in the liver, spleen, and kidneys as confirmed by MRI 24 h post injection. Furthermore, the results obtained from organ measurements were in good agreement with those obtained from SPECT/CT. Conclusions: In conclusion, microbubbles functionalized by different ligands can be labeled with radiotracers and utilized for SPECT/CT imaging, while the incorporation of SPION in MB shells enables imaging using MR. Our investigation revealed that biodistribution may be modified using different ligands. Furthermore, using a single contrast agent with fusion SPECT/CT/MR multimodal imaging enables visualization of functional and anatomical information in one image, thus improving the diagnostic benefit for patients.