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Title: Development of a novel radiation imaging detector system for in vivo gene imaging in small animal studies

Abstract

The authors report preliminary results from a prototype of radiation imaging technology which takes advantage of the emission properties of the radioisotope iodine 125 ({sup 125}I) as the probe. The detector system utilizes crystal scintillators and a position sensitive photomultiplier tube. Iodine 125 decays via electron capture emitting a 35-keV gamma ray with the prompt emission of several 27-32-keV {Kappa} {alpha} and {Kappa} {beta} shell X rays. Because of this, a coincidence condition can be set to detect the {sup 125}I decay, thus reducing background radiation contribution to the image. The prototype detector the authors report has a limited sensitivity and detection area because of the size of the scintillators and photomultiplier tubes, yet it performed well enough to demonstrate the viability of this method for imaging {sup 125}I in a mouse. Mouse imaging studies of iodine uptake by the thyroid and melatonin binding have been done with this detector system using doses of {sup 125}I alone or attached to the melatonin. Many studies in molecular biology follow the expression and regulation of a gene at different stages of an organism`s development or under different physiological conditions. Molecular biology research could benefit from this detection system by utilizing {sup 125}I-labeledmore » gene probes.« less

Authors:
 [1]; ;  [2];  [3]
  1. Thomas Jefferson National Accelerator Facility, Newport News, VA (United States). Detector Group|[Coll. of William and Mary, Williamsburg, VA (United States). Applied Science Dept.
  2. College of William and Mary, Williamsburg, VA (United States). Biology Dept.
  3. Thomas Jefferson National Accelerator Facility, Newport News, VA (United States). Detector Group
Publication Date:
Sponsoring Org.:
USDOE, Washington, DC (United States); National Science Foundation, Washington, DC (United States)
OSTI Identifier:
624073
DOE Contract Number:
AC05-84ER40150
Resource Type:
Journal Article
Resource Relation:
Journal Name: IEEE Transactions on Nuclear Science; Journal Volume: 45; Journal Issue: 3Pt4; Other Information: PBD: Jun 1998
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; IMAGE PROCESSING; GENES; GAMMA CAMERAS; GENE REGULATION; IODINE 125; MICE; PERFORMANCE; DESIGN

Citation Formats

Weisenberger, A.G., Bradley, E.L., Saha, M.S., and Majewski, S. Development of a novel radiation imaging detector system for in vivo gene imaging in small animal studies. United States: N. p., 1998. Web. doi:10.1109/23.685298.
Weisenberger, A.G., Bradley, E.L., Saha, M.S., & Majewski, S. Development of a novel radiation imaging detector system for in vivo gene imaging in small animal studies. United States. doi:10.1109/23.685298.
Weisenberger, A.G., Bradley, E.L., Saha, M.S., and Majewski, S. 1998. "Development of a novel radiation imaging detector system for in vivo gene imaging in small animal studies". United States. doi:10.1109/23.685298.
@article{osti_624073,
title = {Development of a novel radiation imaging detector system for in vivo gene imaging in small animal studies},
author = {Weisenberger, A.G. and Bradley, E.L. and Saha, M.S. and Majewski, S.},
abstractNote = {The authors report preliminary results from a prototype of radiation imaging technology which takes advantage of the emission properties of the radioisotope iodine 125 ({sup 125}I) as the probe. The detector system utilizes crystal scintillators and a position sensitive photomultiplier tube. Iodine 125 decays via electron capture emitting a 35-keV gamma ray with the prompt emission of several 27-32-keV {Kappa} {alpha} and {Kappa} {beta} shell X rays. Because of this, a coincidence condition can be set to detect the {sup 125}I decay, thus reducing background radiation contribution to the image. The prototype detector the authors report has a limited sensitivity and detection area because of the size of the scintillators and photomultiplier tubes, yet it performed well enough to demonstrate the viability of this method for imaging {sup 125}I in a mouse. Mouse imaging studies of iodine uptake by the thyroid and melatonin binding have been done with this detector system using doses of {sup 125}I alone or attached to the melatonin. Many studies in molecular biology follow the expression and regulation of a gene at different stages of an organism`s development or under different physiological conditions. Molecular biology research could benefit from this detection system by utilizing {sup 125}I-labeled gene probes.},
doi = {10.1109/23.685298},
journal = {IEEE Transactions on Nuclear Science},
number = 3Pt4,
volume = 45,
place = {United States},
year = 1998,
month = 6
}
  • Many studies in molecular biology deal with following the expression and regulation of a gene at different stages of an organism`s development or under different physiological conditions. Presently in situ hybridization and immunochemical assays are available to follow the gene expression at a single moment in time for one organism. One must sacrifice the organism to make a measurement, essentially taking a snap shot of the state of expression of the gene of interest. We have made progress on a new type of gene imaging technology which takes advantage of the emission properties of the radioisotope iodine 125 ({sup 125}I)more » as the probe and utilizes crystal scintillators and a position sensitive photomultiplier tube. Iodine 125 decays via electron capture emitting a 35 keV gamma-ray with the prompt emission of several 27-32 keV K{alpha} and K{beta} shell X-rays. Because of this a coincidence condition can be set to detect the {sup 125}I decays thus reducing background radiation contribution to the image. Mouse imaging studies of iodine uptake by the thyroid and melatonin receptor binding have been done with this detector system using low doses of {sup 125}I.« less
  • We propose a design for a high-resolution single-photon emission computed tomography (SPECT) system for in vivo {sup 125}I imaging in small animal using pixellated lithium-drifted silicon (Si(Li)) detectors. The proposed detectors are expected to have high interaction probability (>90%), good energy resolution (<15% FWHM), and good intrinsic spatial resolution ({approx}1 mm FWHM). The SPECT system will consist of a dual head detector geometry with the distance between the detectors ranging 30-50 mm to minimize the imaging distance between the mouse and the detectors. The detectors, each with an active area of 64 mm x 40 mm (64 x 40 arraymore » of 1 mm{sup 2} pixels and a 6 mm thick Si(Li) detector), will be mounted on a rotating gantry with an axial field-of-view of 64 mm. The detector signals will be read out by custom application-specific integrated circuits (ASICs). Using a high-resolution parallel-hole collimator, the expected spatial resolution is 1.6 mm FWHM at an imaging distance of 20 mm, and sensitivity is 6.7 cps/{micro}Ci. {sup 125}I is a readily available radioisotope with a long half-life of 59.4 days and it is commonly used to label biological compounds in molecular biology. Conventional gamma cameras are not optimized to detect the low emission energies (27 to 35 keV) of {sup 125}I. However, Si(Li) detector provides an ideal solution for detecting the low-energy emissions of {sup 125}I. In addition to presenting the design of the system, this paper presents a feasibility study of using Si(Li) detectors to detect the emissions of {sup 125}I.« less
  • The authors report on the development of a high resolution radiation imaging system which is capable of detecting and imaging the coincident gamma and X-ray emissions of the radioisotope iodine 125 ({sup 125}I). Iodine 125 is commonly available as a radioactive label to tag molecular biology probes. Iodine 125 decays via electron capture emitting a 35 keV gamma-ray with the prompt emission of several 27-32 keV X-rays. A coincidence condition can be set to detect the {sup 125}I decays thus reducing background radiation contribution to the image. They are testing the use of arrays of CsI(Na) crystal scintillators coupled tomore » position sensitive photomultiplier tubes for this application. Laboratory studies have thus far been done on mice using a prototype of the detector which is intended to be used to image gene expression in live mice to advance research in neurobiology.« less
  • The use of small animal models in basic and preclinical sciences constitutes an integral part of testing new pharmaceutical agents prior to commercial translation to clinical practice. Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. Biomedical imaging is now listed along with genomics, proteomics, and metabolomics as an integral part of biological and medical sciences. Miniaturized versions of clinical diagnostic modalities, including but not limited to microcomputed tomography, micromagnetic resonance tomography, microsingle-photon-emission tomography, micropositron-emission tomography, optical imaging, digital angiography, and ultrasound,more » have all greatly improved our investigative abilities to longitudinally study various experimental models of human disease in mice and rodents. After an exhaustive literature search, the authors present a concise and critical review of in vivo small animal imaging, focusing on currently available modalities as well as emerging imaging technologies on one side and molecularly targeted contrast agents on the other. Aforementioned scientific topics are analyzed in the context of cancer angiogenesis and innovative antiangiogenic strategies under-the-way to the clinic. Proposed hybrid approaches for diagnosis and targeted site-specific therapy are highlighted to offer an intriguing glimpse of the future.« less
  • In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. Furthermore, such high-resolution systems have relatively poor sensitivity (typically 0.01% to 0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatialmore » resolution, linearity, detection limits, and uniformity. With 99mTc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system’s linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using 99mTc MAG-3 and a thyroid scan with 123I) and one plant study (a 99mTcO 4- xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. In conclusion, UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.« less