Mr. Daiki Hara Profile

Daiki Hara

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Proceedings Article | 4 April 2022 Presentation + Paper

Ex-vivo quantification and localization of PSMA-targeted GNPs via x-ray fluorescence imaging

Daiki Hara, Wensi Tao, Nesrin Dogan, Alan Pollack, John Ford, Junwei Shi

Proceedings Volume 12036, 120361J (2022) https://doi.org/10.1117/12.2612981

KEYWORDS: Tumors, Tissues, Nanoparticles, X-ray fluorescence spectroscopy, Gold, Computed tomography, Imaging systems, X-rays, Spleen, X-ray imaging

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Gold nanoparticles (GNPs) are widely studied in medical research due to their favorable biocompatibility, variety in shape and size, and simple surface modification. Nanoparticles are particularly valuable in cancer research due to their enhanced permeation and retention effect property whereby nanoparticles accumulate in tumors. However, imaging GNPs are a challenge for most imaging modalities. Therefore, recent studies using x-ray fluorescence (XRF) imaging offer a potential for precise quantification and localization of GNPs without single endpoint studies such as immunohistochemistry and mass spectrometry. This study aims to accurately quantify and localize GNPs in ex-vivo tissue from GNP injected mice. 15-nm PEGylated GNPs were conjugated to anti-PSMA antibodies using 1-Ethyl-3-(3- dimethylaminopropyl) carbodiimide and N-hydroxy sulfosuccinimide. 3 SCID mice per group bearing subcutaneous LNCaP xenografts were intravenously injected with either anti-PSMA antibody conjugated GNPs (15mg/mL, 200μL) or Mouse IgG GNPs 24hrs prior to dissection. 11 organs along with the tumor were collected from the mice. Each organs’ GNP content was measured for quantification and localization via XRF on an in-house-developed dual-modality computed tomography and XRF system. Following imaging, organs were dehydrated and dissolved for quantification with inductively coupled plasma mass spectrometry analysis. XRF imaging quantified GNPs in tissue down to 25ng/g. Quantification with XRF imaging showed ~2x times greater accumulation of GNPs in the tumor with anti-PSMA targeted GNPs compared to Mouse IgG control GNPs. Additionally, XRF imaging of anti-PSMA targeted GNPs in all organs showed accurate quantification when compared to ICPMS analysis. XRF computed tomography further confirmed quantification of GNPs in tumors and spleen. This study confirmed the viability of XRF imaging for accurate quantification of anti-PSMA targeted GNPs in ex-vivo tissues.

Proceedings Article | 4 April 2022 Presentation + Paper

Cone-beam x-ray fluorescence imaging using pixelated cadmium telluride photon-counting detector with pinhole collimator

Junwei Shi, Daiki Hara, Ryder Schmidt, Wensi Tao, Nesrin Dogana, John Chetley Ford, Alan Pollack

Proceedings Volume 12036, 120360X (2022) https://doi.org/10.1117/12.2605930

KEYWORDS: Sensors, Imaging systems, Collimators, In vivo imaging, X-ray fluorescence spectroscopy, X-rays, Photodetectors, Nanoparticles, Gold, X-ray imaging

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Gold nanoparticles (GNPs) as promising radiation sensitizers have been increasingly studied in a wide range of radiotherapy applications. By detecting the characteristic x-ray fluorescence (XRF) photons, x-ray fluorescence computed tomography (XFCT) can simultaneously determine both the spatial distribution and concentration of GNPs in vivo, affording for cancer diagnosis and irradiation guidance. However, the long scanning time of current single-pixel detectorbased configuration hinders the translation of XFCT to preclinical and clinical applications. This study presents a conebeam XFCT system using pixelated photon-counting detector with pinhole collimator to acquire XRF projection image in one motion, eliminating the previously step-by-step translation of objects, which allows fast whole-body GNP imaging. We have 3D printed a heat-resistance mold kit to cast a cone-beam x-ray source collimator using Cerrobend alloy. We selected HECITEC (High Energy X-ray Imaging Technology) as the XRF detector, in view of its high spatial resolution (0.25 mm of pitch) and energy resolution (800 eV FWHM at 60 keV). We have customized a 2-mm pinhole collimator to provide spatial information of XRF signals. We have also evaluated the roles of pixel binning and spectrum denoising in aspects of XRF peal extraction. Phantom experiments with GNP of different concentrations (0.078~2.5wt.%) were used to evaluate the sensitivity of GNP detection. In vivo experiments on mouse intravenously administered GNPs were used to validate the feasibility of the proposed system in terms of GNP biodistribution imaging. The results of this study will be helpful to guide XFCT development for routine in vivo GNP imaging

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