Dataset Information

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy.

ABSTRACT: Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and computed tomography (CT) imaging. AuNPs absorb x-rays and subsequently release low-energy, short-range photoelectrons during external beam radiation therapy (RT), increasing the local radiation dose. When AuNPs are near tumor vasculature, the additional radiation dose can lead to increased vascular permeability. This work focuses on understanding how tumor vascular permeability is influenced by AuNP-augmented RT, and how this effect can be used to improve the delivery of nanoparticle chemotherapeutics. Methods: Dual-energy CT was used to quantify the accumulation of both liposomal iodine and AuNPs in tumors following AuNP-augmented RT in a mouse model of primary soft tissue sarcoma. Mice were injected with non-targeted AuNPs, RGD-functionalized AuNPs (vascular targeting), or no AuNPs, after which they were treated with varying doses of RT. The mice were injected with either liposomal iodine (for the imaging study) or liposomal doxorubicin (for the treatment study) 24 hours after RT. Increased tumor liposome accumulation was assessed by dual-energy CT (iodine) or by tracking tumor treatment response (doxorubicin). Results: A significant increase in vascular permeability was observed for all groups after 20 Gy RT, for the targeted and non-targeted AuNP groups after 10 Gy RT, and for the vascular-targeted AuNP group after 5 Gy RT. Combining targeted AuNPs with 5 Gy RT and liposomal doxorubicin led to a significant tumor growth delay (tumor doubling time ~ 8 days) compared to AuNP-augmented RT or chemotherapy alone (tumor doubling time ~3-4 days). Conclusions: The addition of vascular-targeted AuNPs significantly improved the treatment effect of liposomal doxorubicin after RT, consistent with the increased liposome accumulation observed in tumors in the imaging study. Using this approach with a liposomal drug delivery system can increase specific tumor delivery of chemotherapeutics, which has the potential to significantly improve tumor response and reduce the side effects of both RT and chemotherapy.

SUBMITTER: Ashton JR

PROVIDER: S-EPMC5858500 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy.

Ashton Jeffrey R JR Castle Katherine D KD Qi Yi Y Kirsch David G DG West Jennifer L JL Badea Cristian T CT

Theranostics 20180212 7

Gold nanoparticles (AuNPs) are emerging as promising agents for both cancer therapy and computed tomography (CT) imaging. AuNPs absorb x-rays and subsequently release low-energy, short-range photoelectrons during external beam radiation therapy (RT), increasing the local radiation dose. When AuNPs are near tumor vasculature, the additional radiation dose can lead to increased vascular permeability. This work focuses on understanding how tumor vascular permeability is influenced by AuNP-augmented ...[more]

PMID: 29556356

Similar Datasets

Project description:To evaluate the image quality of virtual monochromatic images synthesized from dual-source dual-energy computed tomography (CT) in comparison with conventional polychromatic single-energy CT for the same radiation dose.In dual-energy CT, besides the material-specific information, one may also synthesize monochromatic images at different energies, which can be used for routine diagnosis similar to conventional polychromatic single-energy images. In this work, the authors assessed whether virtual monochromatic images generated from dual-source CT scanners had an image quality similar to that of polychromatic single-energy images for the same radiation dose. First, the authors provided a theoretical analysis of the optimal monochromatic energy for either the minimum noise level or the highest iodine contrast to noise ratio (CNR) for a given patient size and dose partitioning between the low- and high-energy scans. Second, the authors performed an experimental study on a dual-source CT scanner to evaluate the noise and iodine CNR in monochromatic images. A thoracic phantom with three sizes of attenuating rings was used to represent four adult sizes. For each phantom size, three dose partitionings between the low-energy (80 kV) and the high-energy (140 kV) scans were used in the dual-energy scan. Monochromatic images at eight energies (40 to 110 keV) were generated for each scan. Phantoms were also scanned at each of the four polychromatic single energy (80, 100, 120, and 140 kV) with the same radiation dose.The optimal virtual monochromatic energy depends on several factors: phantom size, partitioning of the radiation dose between low- and high-energy scans, and the image quality metrics to be optimized. With the increase of phantom size, the optimal monochromatic energy increased. With the increased percentage of radiation dose on the low energy scan, the optimal monochromatic energy decreased. When maximizing the iodine CNR in monochromatic images, the optimal energy was lower than that when minimizing noise level. When the total radiation dose was equally distributed between low and high energy in dual-energy scans, for minimum noise, the optimal energies were 68, 71, 74, and 77 keV for small, medium, large, and extra-large (xlarge) phantoms, respectively; for maximum iodine CNR, the optimal energies were 66, 68, 70, 72 keV. With the optimal monochromatic energy, the noise level was similar to and the CNR was better than that in a single-energy scan at 120 kV for the same radiation dose. Compared to an 80 kV scan, however, the iodine CNR in monochromatic images was lower for the small, medium, and large phantoms.In dual-source dual-energy CT, optimal virtual monochromatic energy depends on patient size, dose partitioning, and the image quality metric optimized. With the optimal monochromatic energy, the noise level was similar to and the iodine CNR was better than that in 120 kV images for the same radiation dose. Compared to single-energy 80 kV images, the iodine CNR in virtual monochromatic images was lower for small to large phantom sizes.

Project description:PurposeTo provide additional functional information for tumor characterization, we investigated the use of dual-energy computed tomography for imaging murine lung tumors. Tumor blood volume and vascular permeability were quantified using gold and iodine nanoparticles. This approach was compared with a single contrast agent/single-energy CT method. Ex vivo validation studies were performed to demonstrate the accuracy of in vivo contrast agent quantification by CT.MethodsPrimary lung tumors were generated in LSL-Kras(G12D); p53(FL/FL) mice. Gold nanoparticles were injected, followed by iodine nanoparticles two days later. The gold accumulated in tumors, while the iodine provided intravascular contrast. Three dual-energy CT scans were performed-two for the single contrast agent method and one for the dual contrast agent method. Gold and iodine concentrations in each scan were calculated using a dual-energy decomposition. For each method, the tumor fractional blood volume was calculated based on iodine concentration, and tumor vascular permeability was estimated based on accumulated gold concentration. For validation, the CT-derived measurements were compared with histology and inductively-coupled plasma optical emission spectroscopy measurements of gold concentrations in tissues.ResultsDual-energy CT enabled in vivo separation of gold and iodine contrast agents and showed uptake of gold nanoparticles in the spleen, liver, and tumors. The tumor fractional blood volume measurements determined from the two imaging methods were in agreement, and a high correlation (R(2) = 0.81) was found between measured fractional blood volume and histology-derived microvascular density. Vascular permeability measurements obtained from the two imaging methods agreed well with ex vivo measurements.ConclusionsDual-energy CT using two types of nanoparticles is equivalent to the single nanoparticle method, but allows for measurement of fractional blood volume and permeability with a single scan. As confirmed by ex vivo methods, CT-derived nanoparticle concentrations are accurate. This method could play an important role in lung tumor characterization by CT.

Dataset Information

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy.

Publications

Dual-Energy CT Imaging of Tumor Liposome Delivery After Gold Nanoparticle-Augmented Radiation Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets