The aim of this study is to develop a magnetic resonance imaging (MRI)-based treatment planning procedure for intracranial lesions. The method relies on (a) distortion correction of raw magnetic resonance (MR) images by using an adaptive thresholding and iterative technique, (b) autosegmentation of head structures relevant to dosimetric calculations (scalp, bone and brain) using an atlas-based software and (c) conversion of MR images into computed tomography (CT)-like images by assigning bulk CT values to organ contours and dose calculations performed in Eclipse (Philips Medical Systems). Standard CT + MRI-based and MRI-only plans were compared by means of isodose distributions, dose volume histograms and several dosimetric parameters. The plans were also ranked by using a tumor control probability (TCP)-based technique for heterogeneous irradiation, which is independent of radiobiological parameters. For our 3 T Intera MRI scanner (Philips Medical Systems), we determined that the total maximum image distortion corresponding to a typical brain study was about 4 mm. The CT + MRI and MRI-only plans were found to be in good agreement for all patients investigated. Following our clinical criteria, the TCP-based ranking tool shows no significant difference between the two types of plans. This indicates that the proposed MRI-based treatment planning procedure is suitable for the radiotherapy of intracranial lesions.
e biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenogra model Abstract Purpose: Gold nanoparticles (GNPs) have attracted signi cant attention in the treatment of cancer due to their potential as novel radiation enhancers, particularly when functionalized with various targeting ligands. e aim of this study was to assess the biodistribution and pharmacokinetic characteristics of a novel choline-bound GNP (choline-GNP) stabilized with polyethelenimine (PEI).Methods: Choline bound to 27 nm diameter GNPs was characterized using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Toxicity of choline-GNPs was examined on DU-145 prostate cancer cells using an MTT assay. Using balb/c mice bearing ank DU-145 prostate tumors, choline-GNPs bio-distribution was measured using inductively coupled mass spectroscopy (ICP-MS). Blood, heart, lung, liver, spleen, brain, kidney and tumor gold content were examined at multiple time points over a 24-hour period a er tail vein injection.Results: An MTT assay using DU-145 prostate cancer cells yielded a 95% cell viability 72 hours a er choline-GNP administration. e tumor GNP area under the concentrationtime curve during the rst 4 hours (AUC0-4) was 2.2 µg/ml h, representing 13% of the circulating blood GNP concentration over the same time period. e maximum intratumor GNP concentration observed was 1.4% of the injected dose per gram of tumor tissue (%ID/g) one hour post injection.Conclusions: GNPs functionalized with choline demonstrates a viable future nanoparticle platform with increased intra-tumor uptake as compared to unconjugated GNPs. Decreased intra-hepatic accumulation appears to be the reason for the improved systemic bioavailability. e next logical translational investigation will incorporate external beam radiation with the observed maximum intra-tumor uptake.
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