Fluorocapsules for Improved Function, Immunoprotection, and Visualization of Cellular Therapeutics With MR, US, and CT Imaging

Radiology. 2011 Jan;258(1):182-91. doi: 10.1148/radiol.10092339. Epub 2010 Oct 22.

Abstract

Purpose: To develop novel immunoprotective alginate microcapsule formulations containing perfluorocarbons (PFCs) that may increase cell function, provide immunoprotection for xenografted cells, and simultaneously enable multimodality imaging.

Materials and methods: All animal experiments were approved by an Institutional Animal Care and Use Committee. Cadaveric human islet cells were encapsulated with alginate, poly-l-lysine, and perfluorooctyl bromide (PFOB) or perfluoropolyether (PFPE). In vitro viability and the glucose-stimulation index for insulin were determined over the course of 2 weeks and analyzed by using a cross-sectional time series regression model. The sensitivity of multimodality (computed tomography [CT], ultrasonography [US], and fluorine 19 [(19)F] magnetic resonance [MR] imaging) detection was determined for fluorocapsules embedded in gel phantoms. C57BL/6 mice intraperitoneally receiving 6000 PFOB-labeled (n = 6) or 6000 PFPE-labeled (n = 6) islet-containing fluorocapsules and control mice intraperitoneally receiving 6000 PFOB-labeled (n = 6) or 6000 PFPE-labeled (n = 6) fluorocapsules without islets were monitored for human C-peptide (insulin) secretion during a period of 55 days. Mice underwent (19)F MR imaging at 9.4 T and micro-CT. Swine (n = 2) receiving 9000 PFOB capsules through renal artery catheterization were imaged with a clinical multidetector CT scanner. Signal intensity was evaluated by using a paired t test.

Results: Compared with nonfluorinated alginate microcapsules, PFOB fluorocapsules increased insulin secretion of encapsulated human islets, with values up to 18.5% (3.78 vs 3.19) at 8-mmol/L glucose concentration after 7 days in culture (P < .001). After placement of the immunoprotected encapsulated cells into mice, a sustained insulin release was achieved with human C-peptide levels of 19.1 pmol/L ± 0.9 (standard deviation) and 33.0 pmol/L ± 1.0 for PFPE and PFOB capsules, respectively. Fluorocapsules were readily visualized with (19)F MR imaging, US imaging, and CT with research- and clinical-grade imagers for all modalities.

Conclusion: Fluorocapsules enhance glucose responsiveness and insulin secretion in vitro, enable long-term insulin secretion by xenografted islet cells in vivo, and represent a novel contrast agent platform for multimodality imaging.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alginates / pharmacology
  • Animals
  • Capsules / pharmacology*
  • Cross-Sectional Studies
  • Fluorine
  • Fluorocarbons / pharmacology*
  • Humans
  • Islets of Langerhans Transplantation*
  • Magnetic Resonance Imaging / methods
  • Mice
  • Phantoms, Imaging
  • Regression Analysis
  • Swine
  • Ultrasonography / methods
  • X-Ray Microtomography / methods

Substances

  • Alginates
  • Capsules
  • Fluorocarbons
  • Fluorine