Browsing by Subject "Diagnostic Imaging"
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Item Development of Iron Oxide Based Nanoparticles as Dual-Modality Imaging Probes(2008-09-12) Guo, Yi; Sun, XiankaiDual-modality (MR/nuclear) imaging can combine exquisite anatomical resolution with superior molecular sensitivity, and significantly facilitate the accuracy of cancer diagnosis. However, the application of this technique is hampered by the paucity of sensitive dual-modality imaging probes that target tumors specifically. Here we synthesized dual-modality imaging probes by doping positron- or gamma-emitting nuclides to the core of dextran-coated superparamagnetic iron oxide nanoparticles (NUSPIONs). The synthesized nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), atomic force microscope (AFM), and high performance liquid chromatography (HPLC). The evaluations of these nanoparticles were performed both in vitro and in vivo. Four radioisotopes (111In, 177Lu, 64Cu, and 77As) were successfully incorporated into the core of nanoparticles. The purification of nanoparticles via centricon filter accelerated the separation process effectively without apparent aggregation. These nanoparticles exhibited good in vitro stability in both phosphate buffered saline (> 99% intact) and rat serum (> 92% intact) out to 72 h, and the high r2-to-r1 ratio indicating their potential as MRI T2 contrast agents. Two distinctly sized 177Lu-doped nanoparticles (NUSPION-1 and NUSPION-2 with hydrodynamic radii of 11.8 3 nm and 30.6 5 nm respectively) were used for biodistribution studies in normal mice. NUSPION-1 showed significantly (p < 0.0001) higher uptake and longer retention in blood and less uptake in liver and spleen than NUSPION-2, which is advantageous for both passive and active targeting. Due to its optimal tissue distribution pattern, NUSPION-1 was chosen for further in vivo evaluation in PC-3 tumor-bearing mice. High tumor uptake and contrast ratios of tumor-to-muscle and tumor-to-blood were observed. A proof-of-principle dual-modality imaging study was carried out by a virtually single-dose injection in PC-3 tumor-bearing mice. The tumors were visualized by both MRI and autoradiography. Post-MRI Prussian blue iron staining and post-autoradiographic imaging biodistribution confirmed the accumulation of nanoparticles in tumors. Taken together, we have demonstrated a practical method to develop iron oxide based MRI/nuclear imaging probes.Item Evaluation of the Light Emission Kinetics in Luciferin/Luciferase-Based In Vivo Bioluminescence Imaging for Guidance in the Development of Small Animal Imaging Study Design(2006-05-15) Bollinger, Robert Albin; Mason, Ralph P.Bioluminescence imaging (BLI) is gaining acceptance as a small animal imaging modality useful for visualizing cellular and molecular activity in vivo, and especially for evaluating tumor development and efficacies of treatments. Various studies have validated the technique for a number of purposes, including the quantification of tumor burden; however, many basic questions have not been investigated whose answers may ultimately impact the conclusions drawn from the results. Primarily, consideration of the impact of BLI emission kinetics has not been rigorously addressed. This study provides information on the effects of different routes of luciferin substrate injection on the BLI kinetic profile, including time to peak emission, magnitude of peak emission, and emission decay characteristics. This study also presents for the first time the use of subcutaneous (s.c.) luciferin injection and the use of s.c. luciferin injection followed by continuous s.c. infusion (s.c.i.) for establishment of stable BLI light emission. Further, results are presented of the kinetic profile changes associated with 1) inhaled and injected anesthesia; and 2) ambient air heating on mouse core temperature. The study demonstrated substantial differences in the peak light emission with i.v. providing the highest, with s.c., s.c.i. and i.p yielding 30% or less of the light emission of the i.v. route. The correlations between tumor burden and BLI light emission were moderately strong (R>0.75) for each administration route, but at varying times following injection, providing information for establishment of optimal image start times. Surprisingly, ambient cooling of the animal while under anesthesia yielded peak light emissions of up to 100% higher than those obtained when ambient air heating was used to maintain mouse core temperature. Finally, guidelines are presented to aid investigators in development of BLI study design to give due consideration to luciferin administration routes, anesthesia protocol, and animal temperature maintenance.