Hybrid PET/MRI Nanoparticle Development and Multi-Modal Imaging [thesis]

David Hoffman
2013
The development of hybrid PET/MRI imaging systems needs to be paralleled with the development of a hybrid intrinsic PET/MRI probes. The aim of this work was to develop and validate a novel radio-superparamagnetic nanoparticle (r-SPNP) for hybrid PET/MRI imaging. This was achieved with the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) that intrinsically incorporated 59 Fe and manganese iron oxide nanoparticles (MIONs) that intrinsically incorporated 52 Mn. Both [ 59 Fe]-SPIONs
more » ... oth [ 59 Fe]-SPIONs and [ 52 Mn]-MIONs were produced through thermal decomposition synthesis. The physiochemical characteristics of the r-SPNPs were assessed with TEM, DLS, and zeta-potential measurements, as well as in imaging phantom studies. The [ 59 Fe]-SPIONs were evaluated in vivo with biodistribution and MR imaging studies. The biodistrubution studies of [ 59 Fe]-SPIONs showed uptake in the liver. This corresponded with major MR signal contrast measured in the liver. 52 Mn was produced on natural chromium through the 52 Cr(p,n) 52 Mn reaction. The manganese radionuclides were separated from the target material through a liquid-liquid extraction. The α V β 3 integrin binding of [ 52 Mn]-MION-cRGDs was evaluated with α V β 3 integrin solid phase assays, and the expression of α V β 3 integrin in U87MG xenograft tumors was characterized with fluorescence flow cytometry. [ 52 Mn]-MIONiv cRGDs were used for in vivo PET and MR imaging of U87MG xenograft tumor bearing mice. PET data showed increased [ 52 Mn]-MION-cRGD uptake compared with untargeted [ 52 Mn]-MIONs. ROI analysis of PET and MRI data showed that MR contrasted corresponded with PET signal. Future work will utilize [ 52 Mn]-MION-cRGDs in other tumor models and with hybrid PET/MRI imaging systems. v Acknowledgement The first acknowledgement is traditionally, and in this case correctly, made to one's mentor. Jamal Zweit has been a tremendous supervisor for me these past four year and I am grateful for his guidance and criticism. Dr. Zweit has given me opportunities to develop as a scholar that surpass the norm and even my own expectations. I am truly thankful to have Dr. Zweit as my mentor.
doi:10.25772/dx5d-vv92 fatcat:zmyyoqbc3veovbrdemeymqdxh4