Preclinical Evaluation of gold-DTDTPA Nanoparticles As Theranostic Agents in Prostate Cancer Radiotherapy

Butterworth, Karl T.; Nicol, James R; Ghita, Mihaela; Rosa, Soraia; Chaudhary, Pankaj; McGarry, Conor K.; McCarthy, Helen; Jiménez-Sánchez, Gloria; Bazzi, Rana; Roux, Stéphane; Tillement, Olivier; Coulter, Jonathan A.; Prise, Kevin M.

doi:10.2217/nnm-2016-0062

Cited by 43 publications

(30 citation statements)

References 43 publications

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“…Gold nanoparticles are being explored in many applications in the biomedical field such as contrast agents for medical imaging 11,14 , drug delivery, targeted killing of cells 21 and also therapeutic applications, such as theranostic agents 37 and radiosensitization 38 . This has led to numerous investigations of their toxicity and biodistribution.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo

et al. 2017

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Spectral photon counting computed tomography (SPCCT) is an emerging medical imaging technology. SPCCT scanners record the energy of incident photons, which allows specific detection of contrast agents due to measurement of their characteristic x-ray attenuation profiles. This approach is known as K-edge imaging. Nanoparticles formed from elements such as gold, bismuth or ytterbium have been reported as potential contrast agents for SPCCT imaging. Furthermore, gold nanoparticles have many applications in medicine, such as adjuvants for radiotherapy and photothermal ablation. Specific, longitudinal imaging of the biodistribution of nanoparticles would be highly attractive for their clinical translation. We therefore studied the capabilities of a novel SPCCT scanner to quantify the biodistribution of gold nanoparticles in vivo. PEGylated gold nanoparticles were used. Phantom imaging showed that concentrations measured on gold images correlated well with known concentrations (slope = 0.94, intercept = 0.18, RMSE = 0.18, R2 = 0.99). The SPCCT system allowed repetitive and quick acquisitions in vivo, and follow-up of changes in the AuNP biodistribution over time. Measurements performed on gold images correlated with the Inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements in the organs of interest (slope = 0.77, intercept = 0.47, RMSE = 0.72, R2 = 0.93). TEM agreed with the imaging and ICP-OES in that much higher concentrations of AuNP were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT is capable of repetitive and non invasive determination of the biodistribution of gold nanoparticles in vivo.

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Section: Resultsmentioning

confidence: 99%

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo

et al. 2017

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“…Au nanoparticle was also studied as a drug-delivery platform in transient anti-angiogenic therapies to induce tumour vascular normalization and enhance the efficacy of the cytotoxic drugs[15]. Moreover, tumour radiosensitizations for breast and prostate with Au nanoparticle addition were studied both in vitro and in vivo based on the cell-line and small-animal model[16,17]. …”

Section: Introductionmentioning

confidence: 99%

Radiation dose enhancement in skin therapy with nanoparticle addition: A Monte Carlo study on kilovoltage photon and megavoltage electron beams

Zheng

Chow

2017

WJR

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AIMTo investigated the dose enhancement due to the incorporation of nanoparticles in skin therapy using the kilovoltage (kV) photon and megavoltage (MV) electron beams. Monte Carlo simulations were used to predict the dose enhancement when different types and concentrations of nanoparticles were added to skin target layers of varying thickness.METHODSClinical kV photon beams (105 and 220 kVp) and MV electron beams (4 and 6 MeV), produced by a Gulmay D3225 orthovoltage unit and a Varian 21 EX linear accelerator, were simulated using the EGSnrc Monte Carlo code. Doses at skin target layers with thicknesses ranging from 0.5 to 5 mm for the photon beams and 0.5 to 10 mm for the electron beams were determined. The skin target layer was added with the Au, Pt, I, Ag and Fe2O3 nanoparticles with concentrations ranging from 3 to 40 mg/mL. The dose enhancement ratio (DER), defined as the dose at the target layer with nanoparticle addition divided by the dose at the layer without nanoparticle addition, was calculated for each nanoparticle type, nanoparticle concentration and target layer thickness.RESULTSIt was found that among all nanoparticles, Au had the highest DER (5.2-6.3) when irradiated with kV photon beams. Dependence of the DER on the target layer thickness was not significant for the 220 kVp photon beam but it was for 105 kVp beam for Au nanoparticle concentrations higher than 18 mg/mL. For other nanoparticles, the DER was dependent on the atomic number of the nanoparticle and energy spectrum of the photon beams. All nanoparticles showed an increase of DER with nanoparticle concentration during the photon beam irradiations regardless of thickness. For electron beams, the Au nanoparticles were found to have the highest DER (1.01-1.08) when the beam energy was equal to 4 MeV, but this was drastically lower than the DER values found using photon beams. The DER was also found affected by the depth of maximum dose of the electron beam and target thickness. For other nanoparticles with lower atomic number, DERs in the range of 0.99-1.02 were found using the 4 and 6 MeV electron beams.CONCLUSIONIn nanoparticle-enhanced skin therapy, Au nanoparticle addition can achieve the highest dose enhancement with 105 kVp photon beams. Electron beams, while popular for skin therapy, did not produce as high dose enhancements as kV photon beams. Additionally, the DER is dependent on nanoparticle type, nanoparticle concentration, skin target thickness and energies of the photon and electron beams.

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“…This data is shown in Figure 8 (red squares) and was generated using Clonogenic survival assays following treatment with 0-6 Gray (Gy) 160 kVp x-rays as previously described by Butterworth et al [18]. The survival fractions were calculated as the plating efficiency of the treated group divided by the plating efficiency of the untreated control cells, with error bars representing the standard deviation (SD) (n = 7).…”

Section: Comparison With Wet Laboratory Survival Fraction Resultsmentioning

confidence: 99%

“…The wet laboratory experiments had duration of twelve days and initial populations of 200 to 600 cells. Previously, Butterworth et al [18] showed that all damage to cells would take place within 48 hours (2 days); however, twelve days are required for observable colonies to form. The advantage of computational modelling is that the results can be observed at 48 hours and assumptions made that if cells have survived to 48 hours then they will form colonies by 12 days.…”

Section: Comparison With Wet Laboratory Survival Fraction Resultsmentioning

confidence: 99%

Process Algebra with Layers: Multi-scale Integration Modelling Applied to Cancer Therapy

Scott

Nicol

Coulter

et al. 2017

Computational Intelligence Methods for Bioinformatics and Biostatistics

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Abstract. We present a novel Process Algebra designed for multi-scale integration modelling: Process Algebra with Layers (PAL). The unique feature of PAL is the modularisation of scale into integrated layers: Object and Population. An Object can represent a molecule, organelle, cell, tissue, organ or any organism. Populations hold specific types of Object, for example, life stages, cell phases and infectious states. The syntax and semantics of this novel language are presented. A PAL model of the multi-scale system of cell growth and damage from cancer treatment is given. This model allows the analysis of different scales of the system. The Object and Population levels give insight into the length of a cell cycle and cell population growth respectively. The PAL model results are compared to wet laboratory survival fractions of cells given different doses of radiation treatment [1]. This comparison shows how PAL can be used to aid in investigations of cancer treatment in systems biology.

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Preclinical Evaluation of gold-DTDTPA Nanoparticles As Theranostic Agents in Prostate Cancer Radiotherapy

Abstract: This study demonstrates the potential of Au@DTDTPA to enhance CT-image contrast and simultaneously increases the radiosensitivity of prostate tumors.

Cited by 43 publications

References 43 publications

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo

Radiation dose enhancement in skin therapy with nanoparticle addition: A Monte Carlo study on kilovoltage photon and megavoltage electron beams

Process Algebra with Layers: Multi-scale Integration Modelling Applied to Cancer Therapy

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