title: Quantitative single-particle digital autoradiography with α-particle emitters for targeted radionuclide therapy using the iQID camera.
abstract: OBJECTIVE
  Alpha-emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50-80 μm), causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with α emitters may thus inactivate targeted cells with minimal radiation damage to surrounding tissues. Tools are needed to visualize and quantify the radioactivity distribution and absorbed doses to targeted and nontargeted cells for accurate dosimetry of all treatment regimens utilizing α particles, including RIT and others (e.g., Ra-223), especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, the ionizing-radiation quantum imaging detector (iQID) camera, for use in α-RIT experiments.
  
  
  METHODS
  The iQID camera is a scintillator-based radiation detection system that images and identifies charged-particle and gamma-ray/x-ray emissions spatially and temporally on an event-by-event basis. It employs CCD-CMOS cameras and high-performance computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, the authors evaluated its characteristics for α-particle imaging, including measurements of intrinsic detector spatial resolutions and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 ((211)At) activity distributions in cryosections of murine and canine tissue samples.
  
  
  RESULTS
  The highest spatial resolution was measured at ∼20 μm full width at half maximum and the α-particle background was measured at a rate as low as (2.6 ± 0.5) × 10(-4) cpm/cm(2) (40 mm diameter detector area). Simultaneous imaging of multiple tissue sections was performed using a large-area iQID configuration (ø 11.5 cm). Estimation of the (211)At activity distribution was demonstrated at mBq/μg-levels.
  
  
  CONCLUSIONS
  Single-particle digital autoradiography of α emitters has advantages over traditional film-based autoradiographic techniques that use phosphor screens, in terms of spatial resolution, sensitivity, and activity quantification capability. The system features and characterization results presented in this study show that the iQID is a promising technology for microdosimetry, because it provides necessary information for interpreting alpha-RIT outcomes and for predicting the therapeutic efficacy of cell-targeted approaches using α emitters.
authors.affiliation: Pacific Northwest National Laboratory, Richland, Washington 99354 and College of Optical Sciences, The University of Arizona, Tucson, Arizona 85719.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Miller
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Sofia H L
authors.initials: SH
authors.lastname: Frost
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Shani L
authors.initials: SL
authors.lastname: Frayo
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Kenoyer
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Erlinda
authors.initials: E
authors.lastname: Santos
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Jon C
authors.initials: JC
authors.lastname: Jones
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 and Department of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Department of Radiation Oncology, University of Washington, Seattle, Washington 98195.
authors.forename: Donald K
authors.initials: DK
authors.lastname: Hamlin
authors.affiliation: Department of Radiation Oncology, University of Washington, Seattle, Washington 98195.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wilbur
authors.affiliation: Dade Moeller Health Group, Richland, Washington 99354.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109.
authors.forename: Johnnie J
authors.initials: JJ
authors.lastname: Orozco
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 and Department of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 and Department of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, Washington 98109 and Department of Medicine, University of Washington, Seattle, Washington 98195.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000008:administration & dosage; D001246:Astatine; D001345:Autoradiography / Q000295:instrumentation* / Q000379:methods*; D004285:Dogs; D004867:Equipment Design; D005260:Female; D015902:Gamma Cameras; D017493:Leukocyte Common Antigens / Q000008:administration & dosage; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000276:immunology / Q000528:radiation effects; D008228:Lymphoma, Non-Hodgkin / Q000000981:diagnostic imaging / Q000276:immunology / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D019047:Phantoms, Imaging; D011859:Radiography; D016499:Radioimmunotherapy / Q000295:instrumentation* / Q000379:methods*; D012984:Software
chemical_list: D018951:Antigens, CD20; D017493:Leukocyte Common Antigens; D001246:Astatine