46 research outputs found
Imaging biomarker roadmap for cancer studies.
Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET and ultrasonography biomarkers are used extensively in cancer research and drug development. New IBs need to be established either as useful tools for testing research hypotheses in clinical trials and research studies, or as clinical decision-making tools for use in healthcare, by crossing 'translational gaps' through validation and qualification. Important differences exist between IBs and biospecimen-derived biomarkers and, therefore, the development of IBs requires a tailored 'roadmap'. Recognizing this need, Cancer Research UK (CRUK) and the European Organisation for Research and Treatment of Cancer (EORTC) assembled experts to review, debate and summarize the challenges of IB validation and qualification. This consensus group has produced 14 key recommendations for accelerating the clinical translation of IBs, which highlight the role of parallel (rather than sequential) tracks of technical (assay) validation, biological/clinical validation and assessment of cost-effectiveness; the need for IB standardization and accreditation systems; the need to continually revisit IB precision; an alternative framework for biological/clinical validation of IBs; and the essential requirements for multicentre studies to qualify IBs for clinical use.Development of this roadmap received support from Cancer Research UK and the Engineering and Physical Sciences Research Council (grant references A/15267, A/16463, A/16464, A/16465, A/16466 and A/18097), the EORTC Cancer Research Fund, and the Innovative Medicines Initiative Joint Undertaking (grant agreement number 115151), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in kind contribution
Arrangement of the phosphate- and metal-binding subsites of phospholucomutase. Intersubsite distance by means of nuclear magnetic resonance measurements
Integrating quantitative imaging and computational modeling to predict the spatiotemporal distribution of \u3csup\u3e186\u3c/sup\u3eRe nanoliposomes for recurrent glioblastoma treatment
\u3cp\u3eGlioblastoma multiforme is the most common and deadly form of primary brain cancer. Even with aggressive treatment consisting of surgical resection, chemotherapy, and external beam radiation therapy, response rates remain poor. In an attempt to improve outcomes, investigators have developed nanoliposomes loaded with 186Re, which are capable of delivering a large dose (< 1000 Gy) of highly localized β- radiation to the tumor, with minimal exposure to healthy brain tissue. Additionally, \u3csup\u3e186\u3c/sup\u3eRe also emits gamma radiation (137 keV) so that it's spatio-temporal distribution can be tracked through single photon emission computed tomography. Planning the delivery of these particles is challenging, especially in cases where the tumor borders the ventricles or previous resection cavities. To address this issue, we are developing a finite element model of convection enhanced delivery for nanoliposome carriers of radiotherapeutics. The model is patient specific, informed by each individual's own diffusion-weighted and contrast-enhanced magnetic resonance imaging data. The model is then calibrated to single photon emission computed tomography data, acquired at multiple time points mid- and post-infusion, and validation is performed by comparing model predictions to imaging measurements obtained at future time points. After initial calibration to a one SPECT image, the model is capable of recapitulating the distribution volume of RNL with a DICE coefficient of 0.88 and a PCC of 0.80. We also demonstrate evidence of restricted flow due to large nanoparticle size in comparison to interstitial pore size.\u3c/p\u3