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Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements.

ABSTRACT: The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er(3+) nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents for targeted tumour imaging and irradiation dose enhancers in tumours during radiotherapy. Remarkably, they showed low toxicity and excellent performance in active-targeting CT imaging and CT imaging-guided radiosensitizing therapy, which could greatly concentrate and enlarge the irradiation dose deposition in tumours to enhance therapeutic efficacy and minimize the damage to surrounding tissues.

SUBMITTER: Xing H

PROVIDER: S-EPMC3638198 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements.

Xing Huaiyong H Zheng Xiangpeng X Ren Qingguo Q Bu Wenbo W Ge Weiqiang W Xiao Qingfeng Q Zhang Shengjian S Wei Chenyang C Qu Haiyun H Wang Zheng Z Hua Yanqing Y Zhou Liangping L Peng Weijun W Zhao Kuaile K Shi Jianlin J

Scientific reports 20130101

The clinical potentials of radiotherapy could not be achieved completely because of the inaccurate positioning and inherent radioresistance of tumours. In this study, a novel active-targeting upconversion theranostic agent (arginine-glycine-aspartic acid-labelled BaYbF5: 2% Er(3+) nanocube) was developed for the first time to address these clinical demands. Heavy metal-based nanocubes (~10 nm) are potential theranostic agents with bifunctional features: computed tomography (CT) contrast agents f ...[more]

PMID: 23624542

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Project description:ImportanceMagnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial.ObjectiveTo determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance.Design, setting, and participantsThis phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up.InterventionsPatients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions.Main outcomes and measuresThe primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03-based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)-based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)-based outcomes.ResultsBetween May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P = .01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P = .003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P = .01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P = .001) at 1 month.Conclusions and relevanceIn this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist.Trial registrationClinicalTrials.gov Identifier: NCT04384770.

Project description:BackgroundThe imaging dose of cone-beam computed tomography (CBCT) in image-guided radiotherapy (IGRT) poses adverse effects on patient health. To improve the quality of sparse-view low-dose CBCT images, a projection synthesis convolutional neural network (SynCNN) model is proposed.MethodsIncluded in this retrospective, single-center study were 223 patients diagnosed with brain tumours from Beijing Cancer Hospital. The proposed SynCNN model estimated two pairs of orthogonally direction-separable spatial kernels to synthesize the missing projection in between the input neighboring sparse-view projections via local convolution operations. The SynCNN model was trained on 150 real patients to learn patterns for inter-view projection synthesis. CBCT data from 30 real patients were used to validate the SynCNN, while data from a phantom and 43 real patients were used to test the SynCNN externally. Sparse-view projection datasets with 1/2, 1/4, and 1/8 of the original sampling rate were simulated, and the corresponding full-view projection datasets were restored using the SynCNN model. The tomographic images were then reconstructed with the Feldkamp-Davis-Kress algorithm. The root-mean-square error (RMSE), peak signal-to-noise ratio (PSNR), and structural similarity (SSIM) metrics were measured in both the projection and image domains. Five experts were invited to grade the image quality blindly for 40 randomly selected evaluation groups with a four-level rubric, where a score greater than or equal to 2 was considered acceptable image quality. The running time of the SynCNN model was recorded. The SynCNN model was directly compared with the three other methods on 1/4 sparse-view reconstructions.ResultsThe phantom and patient studies showed that the missing projections were accurately synthesized. In the image domain, for the phantom study, compared with images reconstructed from sparse-view projections, images with SynCNN synthesis exhibited significantly improved qualities with decreased values in RMSE and increased values in PSNR and SSIM. For the patient study, between the results with and without the SynCNN synthesis, the averaged RMSE decreased by 3.4×10-4, 10.3×10-4, and 21.7×10-4, the averaged PSNR increased by 3.4, 6.6, and 9.4 dB, and the averaged SSIM increased by 5.2×10-2, 18.9×10-2 and 33.9×10-2, for the 1/2, 1/4, and 1/8 sparse-view reconstructions, respectively. In expert subjective evaluation, both the median scores and acceptance rates of the images with SynCNN synthesis were higher than those reconstructed from sparse-view projections. It took the model less than 0.01 s to synthesize an inter-view projection. Compared with the three other methods, the SynCNN model obtained the best scores in terms of the three metrics in both domains.ConclusionsThe proposed SynCNN model effectively improves the quality of sparse-view CBCT images at a low time cost. With the SynCNN model, the CBCT imaging dose in IGRT could be reduced potentially.

Dataset Information

Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements.

Publications

Computed tomography imaging-guided radiotherapy by targeting upconversion nanocubes with significant imaging and radiosensitization enhancements.

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