Exploitation of the full potential offered by ion beams in clinical practice is still hampered by several sources of treatment uncertainties, particularly related to limitations of our ability to locate the position of the Bragg peak in the tumour. To this end, several efforts are ongoing to improve the characterization of patient position, anatomy and tissue stopping power properties prior to treatment, as well as to enable in-vivo verification of the actual dose delivery, or at least beam range, during or shortly after treatment. This contribution critically reviews methods under development or clinical testing for verification of ion therapy, based on pre-treatment range and tissue probing as well as detection of secondary emissions or physiological changes during and after treatment, trying to disentangle approaches of general applicability from those more specific to certain anatomical locations. Moreover, it discusses future directions, which could benefit from integration of multiple modalities or address novel exploitation of the measurable signals for biologically adapted therapy.
Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic. Liposomes can compartmentalize and solubilize both hydrophilic and hydrophobic materials. All these properties of liposomes and their flexibility for surface modification to add targeting moieties make liposomes more attractive candidates for use as drug delivery vehicles. There are many novel liposomal formulations that are in various stages of development, to enhance therapeutic effectiveness of new and established drugs that are in preclinical and clinical trials. Recent developments in multimodality imaging to better diagnose disease and monitor treatments embarked on using liposomes as diagnostic tool. Conjugating liposomes with different labeling probes enables precise localization of these liposomal formulations using various modalities such as PET, SPECT, and MRI. In this review, we will briefly review the clinical applications of liposomal formulation and their potential imaging properties.
Contemporary treatment planning systems for proton radiotherapy typically use analytical pencil-beam algorithms - which require a comprehensive set of configuration data - to predict the absorbed dose distributions in the patient. In order to reduce the time required to prepare a new proton treatment planning system for clinical use, it was desirable to configure the planning system before measured beam data were available. However, it was not known if the Monte Carlo simulation method was a practical alternative to measuring beam profiles. The purpose of this study was to develop a model of a passively scattered proton therapy unit, to simulate the properties of the proton fields using the Monte Carlo technique and to configure an analytical treatment planning system using the simulated beam data. Additional simulations and treatment plans were calculated in order to validate the pencil-beam predictions against the Monte Carlo simulations using realistic treatment beams. Comparison of dose distributions in a water phantom revealed small dose difference and distances to agreement under the validation conditions. The total simulation time for generating the 768 beam configuration profiles was approximately 6 weeks using 30 nodes in a parallel processing cluster. The results of this study show that it is possible to configure and test a proton treatment planning system prior to the availability of measured proton beam data. The model presented here provided a means to reduce by several months the time required to prepare an analytical treatment planning system for patient treatments.
Passive beam spreading techniques have been used for most proton therapy treatments worldwide. This delivery method employs static scattering foils to spread the beam laterally and a range modulating wheel or ridge filter to spread the high dose region in depth to provide a uniform radiation dose to the treatment volume. Neutrons produced by interactions of the treatment beam with nozzle components, such as the range modulation wheel, can account for a large portion of the secondary dose delivered to healthy tissue outside the treatment volume. Despite this fact, little is known about the effects of range modulation on the secondary neutron exposures around passively scattered proton treatment nozzles. In this work, the neutron dose equivalent spectra per incident proton (H(E)/p) and total neutron dose equivalent per therapeutic absorbed dose (H/D) were studied using Monte Carlo techniques for various values of range modulation at 54 locations around a passive scattering proton therapy treatment nozzle. As the range modulator wheel step thickness increased from 1.0 to 11.5 cm, the peak values of H(E)/p decreased from approximately 1 x 10(-17) mSv Gy(-1) to approximately 2 x 10(-18) mSv Gy(-1) at 50 cm from isocentre along the beam's central axis. In general, H/D increased with increasing range modulation at all locations studied, and the maximum H/D exposures shifted away from isocentre.
The development and use of sensitizing agents to improve the effectiveness of radiotherapy have long been sought to improve our ability to treat cancer. In this letter, we have studied the relative biological effectiveness of proton beam radiotherapy on prostate tumor cells with and without internalized gold nanoparticles. The effectiveness of proton radiotherapy for the killing of prostate tumor cells was increased by approximately 15%–20% for those cells containing internalized gold nanoparticles.
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