title: High-resolution radioluminescence microscopy of 18F-FDG uptake by reconstructing the β-ionization track.
abstract: Radioluminescence microscopy is a new method for imaging radionuclide uptake by single live cells with a fluorescence microscope. Here, we report a particle-counting scheme that improves spatial resolution by overcoming the β-range limit.
  
  
  METHODS
  Short frames (10 μs-1 s) were acquired using a high-gain camera coupled to a microscope to capture individual ionization tracks. Optical reconstruction of the β-ionization track (ORBIT) was performed to localize individual β decays, which were aggregated into a composite image. The new approach was evaluated by imaging the uptake of (18)F-FDG in nonconfluent breast cancer cells.
  
  
  RESULTS
  After image reconstruction, ORBIT resulted in better definition of individual cells. This effect was particularly noticeable in small clusters (2-4 cells), which occur naturally even for nonconfluent cell cultures. The annihilation and Bremsstrahlung photon background signal was markedly lower. Single-cell measurements of (18)F-FDG uptake that were computed from ORBIT images more closely matched the uptake of the fluorescent glucose analog (Pearson correlation coefficient, 0.54 vs. 0.44, respectively).
  
  
  CONCLUSIONS
  ORBIT can image the uptake of a radiotracer in living cells with spatial resolution better than the β range. In principle, ORBIT may also allow for greater quantitative accuracy because the decay rate is measured more directly, with no dependency on the β-particle energy.
authors.affiliation: Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California.
authors.forename: Guillem
authors.initials: G
authors.lastname: Pratx
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Conroy
authors.initials: C
authors.lastname: Sun
authors.forename: Marian
authors.initials: M
authors.lastname: Axente
authors.forename: Laura
authors.initials: L
authors.lastname: Sasportas
authors.forename: Colin
authors.initials: C
authors.lastname: Carpenter
authors.forename: Lei
authors.initials: L
authors.lastname: Xing
mesh_terms: D001610:Beta Particles; D001692:Biological Transport; D045744:Cell Line, Tumor; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D006801:Humans; D008027:Light; D008853:Microscopy / Q000379:methods*; D057054:Molecular Imaging
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: autoradiography; microscopy; radionuclide imaging instrumentation; single-cell analysis