99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice

Liu, Zhonglin; Stevenson, Gail D.; Barrett, Harrison H.; Kastis, George A.; Bettan, Michel; Furenlid, Lars R.; Wilson, Donald W.; Woolfenden, James M.; Pak, Koon Y.

doi:10.1097/01.mnm.0000130243.06821.90

Cited by 15 publications

(11 citation statements)

References 19 publications

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“…T ODAY, small animal Single Photon Emission Computed Tomography (SPECT) pinhole imaging [1;2] can yield excellent image resolutions [3][4][5] down to the sub-half-mm scale [6;7]. At present these ultra-high resolutions are obtained using traditional gamma cameras, by employing the principle of pinhole magnification.…”

Section: Introductionmentioning

confidence: 99%

Depth-of-interaction detection and correction with a multi-scale algorithm in CCD based gamma cameras

Korevaar

Heemskerk

Goorden

et al. 2008

2008 IEEE Nuclear Science Symposium Conference Record

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Gamma cameras based on Charge Coupled Devices (CCDs) and micro-columnar CsI scintillators can reach high spatial resolutions. However, the gamma interaction probability of these scintillators is low (typically <30% at 141 keV) due to the limited thickness of presently available micro-columnar scintillators. Continuous scintillators can improve the interaction probability but suffer from increased light spread compared to columnar scintillators. In addition, for both types of scintillators gamma photons incident at an oblique angle reduce the spatial resolution due to the variable depth of interaction (DOl). To improve spatial resolution and spectral characteristics of these detectors, we have developed a fast analytic scintillation detection algorithm that makes use of a depth-dependent light spread model and as a result is able to determine the DOl in the scintillator. This algorithm, performing multi-scale frame analysis, was tested for an Electron Multiplying CCD (EM-CCD) optically coupled to CsI(TI) scintillators of different thicknesses.For a 2.6 mm thick scintillator a spatial resolution of 148 J.1m Full Width Half Maximum (FWHM) was obtained with an energy resolution of 46% FWHM for gamma photons incident perpendicularly (interaction probability 61 % at 141 keY). The multi-scale algorithm improves the spatial resolution up to 11 %, and the energy resolution up to 36 % compared to a previously implemented algorithm that did not model the depth-dependent light spread. In addition, the multi-scale algorithm can accurately approximate DOl. As a result, degradation of the spatial resolution due to the variable DOl for gamma photons incident at a 47 0 angle was improved from 2600 Jlm to 508 Jlm FWHM for a 3 mm thick scintillator. We conclude that the multi-scale algorithm significantly improves CCD based gamma cameras as can be applied in future SPECT systems.

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Section: Introductionmentioning

confidence: 99%

Depth-of-interaction detection and correction with a multi-scale algorithm in CCD based gamma cameras

Korevaar

Heemskerk

Goorden

et al. 2008

2008 IEEE Nuclear Science Symposium Conference Record

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“…Glucarate (GLA), a normal metabolite of D-glucuronic acid, is a small, six-carbon dicarboxylic acid compound that is excreted in urine, and has long been used as a stabilizer for calcium gluconate injections. GLA can be labeled by sodium pertechnetate Nuclear Medicine and Biology 42 (2015) 608-613 (Na[ 99m TcO 4 ]), thus forming 99m Tc-GLA [11,15]. Experimental studies suggest that 99m Tc-GLA tends to be concentrated in the heart and brain with local ischemia and early necrosis [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…As a promising 99m Tc-labeled analog, 99m Tc-glucarate ( 99m Tc-GLA) has been investigated in various tumor imaging studies [10][11][12][13][14][15], and has been found to exhibit different pharmacology and pharmacokinetics compared to those of 18 F-FDG. Glucarate (GLA), a normal metabolite of D-glucuronic acid, is a small, six-carbon dicarboxylic acid compound that is excreted in urine, and has long been used as a stabilizer for calcium gluconate injections.…”

Section: Introductionmentioning

confidence: 99%

Investigations of 99mTc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism

Ли

et al. 2015

Nuclear Medicine and Biology

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“…Imaging small-animal models of cancer can illustrate the interaction of the tumor with its microenvironment, but further work is required to generate a sufficient library of imaging agents, because the translation of in vitro assays into SPECT agents is challenging (74). In the case of chemotherapy planning and evaluation for multidrug resistance, small-animal SPECT/CT has characterized several radiopharmaceuticals used to monitor the expression or activity of the transmembrane p-glycoprotein pump, including 99m Tc tetrofosmin, 99m Tc-sestamibi (80), and a Schiff base 67 Ga(III) complex (81), and compared their efflux with that of radiopharmaceuticals resistant to washout by p-glycoprotein-expressing tumors (82). These types of studies require rapid dynamic small-animal SPECT, similar to the need described earlier.…”

Section: Cardiovascular Applicationsmentioning

confidence: 99%

Small-Animal SPECT and SPECT/CT: Important Tools for Preclinical Investigation

Franc¹,

Acton²,

Marì³

et al. 2008

J Nucl Med

207

122

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The need to study dynamic biologic processes in intact smallanimal models of disease has stimulated the development of highresolution nuclear imaging methods. These methods are capable of clarifying molecular interactions important in the onset and progression of disease, assessing the biologic relevance of drug candidates and potential imaging agents, and monitoring therapeutic effectiveness of pharmaceuticals serially within a single-model system. Single-photon-emitting radionuclides have many advantages in these applications, and SPECT can provide 3-dimensional spatial distributions of g-(and x-) ray-emitting radionuclide imaging agents or therapeutics. Furthermore, combining SPECT with CT in a SPECT/CT system can assist in defining the anatomic context of biochemical processes and improve the quantitative accuracy of the SPECT data. Over the past decade, dedicated small-animal SPECT and SPECT/CT systems have been developed in academia and industry. Although significant progress in this arena has been realized through system development and biologic application, further innovation continues to address challenges in camera sensitivity, spatial resolution, and image reconstruction and quantification. The innumerable applications of small-animal SPECT and SPECT/CT in drug development, cardiology, neurology, and oncology are stimulating further investment in education, research, and development of these dedicated small-animal imaging modalities. Rapi dly evolving knowledge of molecular biology has stimulated exploration of novel therapies targeting specific points in molecular pathways associated with cardiac disease, neurologic disorders, cancer, and many other pathologic processes. However, identifying the role of a molecule in a disease process modeled in vitro does not necessarily translate to an understanding of its interactions with other molecular processes in vivo. On the other hand, few of all disease processes can be fully studied in human patients because of logistical and ethical concerns. Small-animal models represent a critical bridge between discoveries at the molecular level and implementation of clinically relevant diagnostics or therapeutics. Emphasis is ever increasing that these models accurately recapitulate both the disease itself and the environment in which the key molecular processes take place. For example, xenograft mouse models of cancer are simple to develop but are not considered particularly useful in understanding molecular interactions involved in carcinogenesis. More sophisticated approaches, such as transgenic models using oncogene activation or tumor suppressor inactivation, have evolved to the point at which cancers may be induced in a spatially and temporally defined manner using deletion of specified genetic sequences with Cre recombinase (1,2). Sophisticated infrastructures have been developed to manage data related to small-animal models of disease and provide greater access to various mouse models for all investigators, exemplified by the Mouse Models of Human Cancer Cons...

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99mTc glucarate high-resolution imaging of drug sensitive and drug resistant human breast cancer xenografts in SCID mice

Cited by 15 publications

References 19 publications

Depth-of-interaction detection and correction with a multi-scale algorithm in CCD based gamma cameras

Depth-of-interaction detection and correction with a multi-scale algorithm in CCD based gamma cameras

Investigations of 99mTc-labeled glucarate as a SPECT radiotracer for non-small cell lung cancer (NSCLC) and potential tumor uptake mechanism

Small-Animal SPECT and SPECT/CT: Important Tools for Preclinical Investigation

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