Christiane Mallett PhD, Presenter: Nothing to Disclose

Dorela D. Shuboni PhD, Abstract Co-Author: Nothing to Disclose

Aaron Schwartz-Duval, Abstract Co-Author: Nothing to Disclose

Eric Swy, Abstract Co-Author: Nothing to Disclose

Matthew T. Latourette BS, Abstract Co-Author: Nothing to Disclose

Maciej Parys DVM, Abstract Co-Author: Nothing to Disclose

David Peter Cormode DPhil, MS, Abstract Co-Author: Research Grant, Koninklijke Philips NV Consultant, Koninklijke Philips NV

Erik M. Shapiro PhD, Abstract Co-Author: Nothing to Disclose

High Z metal nanoparticles (NPs) have the potential to shift the use of CT from structural to molecular imaging. Bismuth (Bi) has a high k-edge, low cost of production and low toxicity. We conducted in vitro and in vivo assays to determine the toxicity, clinical manifestations and imaging efficacy of polymer-encapsulated Bi NPs.

40 nm pure Bi nanocrystals were synthesized and characterized, then encapsulated into poly(lactic-co-glycolic)acid (PLGA) NPs with or without coumarin for fluorescence. In vitro, we assessed Bi nanocrystal and NP dissolution at pH 7 and 5.5 for 42 days and the effect of the NPs on cell proliferation. Ex vivo μCT and fluorescence imaging was performed on a piece of chicken meat injected with NPs. For in vivo toxicology, Sprague-Dawley rats were injected IV or IP with NPs at 2 & 20 mg Bi/kg. Blood was collected for analysis of serum chemistry and hematology, and organs were collected for histopathology. For in vivo μCT, NPs in PBS at 160 or 550 mg/kg were injected retro-orbitally and the mice were scanned 1-24h post-injection.

After 24h, NPs (~120 nm, 60% Bi w/w) were 70% dissolved at pH 5.5; there was negligible dissolution at pH 7 on d42. Cell proliferation was unaffected at the lowest Bi concentrations but was reduced at 10-1000 μg/mL. In vivo, there were no clinically significant changes in blood measures. Histopathology found mild kidney damage and recovery in one rat that received 20 mg/kg NPs IV. Ex vivo, the μCT and coumarin signals were exactly overlaid. With in vivo μCT, Bi contrast was detected in the liver and spleen of the mice. There were some adverse effects at doses ten times higher than anticipated for targeted molecular imaging studies.

Fluorescent/CT dense coumarin-Bi NPs were fabricated and in vivo CT imaging demonstrated. Toxicity was minimal except at high doses. Strategies for reducing the rapid rate of Bi dissolution from Bi-PLGA NPs, and PEG-ylation to reduce renal clearance, should be explored to minimize toxicity at high doses. For molecular imaging with this agent, the particles will be targeted to specific cellular targets and the route of delivery optimized to achieve a high local and lower systemic dose of bismuth.

Polymer encapsulated Bi NPs are a novel technological platform for molecular and cellular CT, and their low cost and minimal toxicity are enabling for potential clinical applications. 

Mallett, C, Shuboni, D, Schwartz-Duval, A, Swy, E, Latourette, M, Parys, M, Cormode, D, Shapiro, E, Dual-Modality, Fluorescent, PLGA-Encapsulated Bismuth Nanoparticles: A Novel Nanoparticle Platform for Molecular and Cellular Computed Tomography.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14007961.html