Quantitative single‐particle digital autoradiography with α‐particle emitters for targeted radionuclide therapy using the iQID camera

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 eventby-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. C 2015 American Association of Physicists in Medicine. [http://dx

Actinide bioimaging in tissues: Comparison of emulsion and solid track autoradiography techniques with the iQID camera

“…A thicker substrate increases lateral spread of scintillation light reaching the detector, which results in a lower spatial resolution due to higher uncertainty of the estimated interaction location. [28]. …”

“…The iQID camera [23, 28] uses a thin film detector made of an inorganic solid scintillator [37], to convert alpha particle energy to a flash of light that is amplified and acquired by a charge-coupled device (CCD) camera. The technical aspects of the iQID camera have already been thoroughly described by Miller et al .…”

“…These recent techniques enable quantification of the activity distribution in tissue sections. They have been increasingly applied for research in targeted alpha radiotherapy [25–28], with derivation of absorbed dose estimates [27]. In the frame of internal contamination with actinides, re-analysis of archival tissues is important to answer new questions that could not be addressed with techniques from the past [29, 30].…”

Updated Liquid Secondary Waste Grout Formulation and Preliminary Waste Form Qualification

“…Single-particle digital autoradiography experiments assessed the spatial distribution of 99 Tc within crosssectioned monolith "pucks" using the ionizing-radiation Quantum Imaging Detector (iQID) (Miller et al 2015). The iQID measures individual β-decay events to produce a digital image in real time.…”

“…The iQID measures individual β-decay events to produce a digital image in real time. According to Miller et al (2015), the iQID imager comprises a scintillator in direct contact with a micro-channel plate image intensifier and a lens for imaging the intensifier screen onto a charge-coupled device (CCD) or complementary metal oxide semiconductor (CMOS) camera sensor, all within a compact light-tight enclosure. Disks sectioned from within ~0.5" from the center of the monoliths were analyzed using the iQID.…”