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Quantitative single-particle digital autoradiography with α-particle emitters for targeted radionuclide therapy using the iQID camera. Med Phys 2015 Jul;42(7):4094-105

Date

07/03/2015

Pubmed ID

26133610

Pubmed Central ID

PMC4464071

DOI

10.1118/1.4921997

Scopus ID

2-s2.0-84935908349 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

PURPOSE: 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.

Author List

Miller BW, Frost SH, Frayo SL, Kenoyer AL, Santos E, Jones JC, Green DJ, Hamlin DK, Wilbur DS, Fisher DR, Orozco JJ, Press OW, Pagel JM, Sandmaier BM

Author

Test W. User test user title in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Antigens, CD20
Astatine
Autoradiography
Dogs
Equipment Design
Female
Gamma Cameras
Leukocyte Common Antigens
Lymph Nodes
Lymphoma, Non-Hodgkin
Mice
Mice, Nude
Neoplasm Transplantation
Phantoms, Imaging
Radiography
Radioimmunotherapy
Software