High-energy beams of charged nuclear particles (protons and heavier ions) offer significant advantages for the treatment of deep-seated local tumors in comparison to conventional megavolt photon therapy. Their physical depth-dose distribution in tissue is characterized by a small entrance dose and a distinct maximum (Bragg peak) near the end of range with a sharp fall-off at the distal edge. Taking full advantage of the well-defined range and the small lateral beam spread, modern scanning beam systems allow delivery of the dose with millimeter precision. In addition, projectiles heavier than protons such as carbon ions exhibit an enhanced biological effectiveness in the Bragg peak region caused by the dense ionization of individual particle tracks resulting in reduced cellular repair. This makes them particularly attractive for the treatment of radio-resistant tumors localized near organs at risk. While tumor therapy with protons is a well-established treatment modality with more than 60 000 patients treated worldwide, the application of heavy ions is so far restricted to a few facilities only. Nevertheless, results of clinical phase I-II trials provide evidence that carbon-ion radiotherapy might be beneficial in several tumor entities. This article reviews the progress in heavy-ion therapy, including physical and technical developments, radiobiological studiesmore » and models, as well as radiooncological studies. As a result of the promising clinical results obtained with carbon-ion beams in the past ten years at the Heavy Ion Medical Accelerator facility (Japan) and in a pilot project at GSI Darmstadt (Germany), the plans for new clinical centers for heavy-ion or combined proton and heavy-ion therapy have recently received a substantial boost.« less

Heavy-ion tumor therapy: Physical and radiobiological benefits

The present paper represents the first clinical report of the use of stereotactically-directed narrow beams of helium ions from the 184-inch Synchrocyclotron at the Lawrence Berkeley Laboratory for the radiosurgical treatment of life-threatening vascular disorders of the brain, including inoperable inaccessible deep arteriovenous malformations (AVMs) and carotid artery-cavernous sinus fistulas (CCFs). We describe the methods developed for stereotactic neuroradiological imaging and stereotactic helium-ion Bragg peak radiosurgery in the evaluation and treatment of the first 55 patients with deep AVMs in a clinical research protocol. We discuss the diagnosis and epidemiological characteristics of the diseases, the neurosurgical and radiosurgical methods of treatment available and the initial experience of stereotactic helium-ion Bragg peak radiosurgery, including stereotactic neuroradiological evaluation, treatment planning, heavy-ion beams, patient treatment protocol, early clinical results, patien...

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Stereotactic heavy-ion Bragg peak radiosurgery for intra-cranial vascular disorders: method for treatment of deep arteriovenous malformations

Since the seventies, positron emission tomography (PET) has become an invaluable medical molecular imaging modality with an unprecedented sensitivity at the picomolar level, especially for cancer diagnosis and the monitoring of its response to therapy. More recently, its combination with x-ray computed tomography (CT) or magnetic resonance (MR) has added high precision anatomic information in fused PET/CT and PET/MR images, thus compensating for the modest intrinsic spatial resolution of PET. Nevertheless, a number of medical challenges call for further improvements in PET sensitivity. These concern in particular new treatment opportunities in the context personalized (also called precision) medicine, such as the need to dynamically track a small number of cells in cancer immunotherapy or stem cells for tissue repair procedures. A better signal-to-noise ratio (SNR) in the image would allow detecting smaller size tumours together with a better staging of the patients, thus increasing the chances of putting cancer in complete remission. Moreover, there is an increasing demand for reducing the radioactive doses injected to the patients without impairing image quality. There are three ways to improve PET scanner sensitivity: improving detector efficiency, increasing geometrical acceptance of the imaging device and pushing the timing performance of the detectors. Currently, some pre-localization of the electron-positron annihilation along a line-of-response (LOR) given by the detection of a pair of annihilation photons is provided by the detection of the time difference between the two photons, also known as the time-of-flight (TOF) difference of the photons, whose accuracy is given by the coincidence time resolution (CTR). A CTR of about 10 picoseconds FWHM will ultimately allow to obtain a direct 3D volume representation of the activity distribution of a positron emitting radiopharmaceutical, at the millimetre level, thus introducing a quantum leap in PET imaging and quantification and fostering more frequent use of 11C radiopharmaceuticals. The present roadmap article toward the advent of 10 ps TOF-PET addresses the status and current/future challenges along the development of TOF-PET with the objective to reach this mythic 10 ps frontier that will open the door to real-time volume imaging virtually without tomographic inversion. The medical impact and prospects to achieve this technological revolution from the detection and image reconstruction point-of-views, together with a few perspectives beyond the TOF-PET application are discussed.

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Roadmap toward the 10 ps time-of-flight PET challenge

A method for the in-situ control of the heavy-ion tumour therapy by means of positron emission tomography is introduced. This method is founded on the measurement of the dynamic spatial distribution of /spl beta//sup +/-emitters generated by nuclear fragmentation during the irradiation and the relationship between the spatial distributions of the /spl beta//sup +/-radioactivity and the dose. In order to study this relationship and to arrive at deducing the dose distribution from the measured /spl beta//sup +/-activity distribution a framework of model calculations is used. Results of phantom experiments with /sup 12/C ion beams are presented, demonstrating the good agreement between experiment and simulation as well as the possibilities and limits of treatment plan verification and beam monitoring.

In-beam PET imaging for the control of heavy-ion tumour therapy

Heavy ion therapy has two definite advantages: good dose localization and higher biological effect. Range calculation of the heavy ions is an important factor in treatment planning. X-ray CT numbers are used to estimate the heavy ion range by looking up values in a conversion table which relates empirically photon attenuation in tissues to particle stopping power; this is one source of uncertainty in the treatment planning. Use of positron emitting radioactive beams along with a positron emission tomograph or a positron camera gives range information and may be used as a means of checking in heavy ion treatment planning. However, the metabolism of the implanted positron emitters in a living object is unpredictable because the chemical forms of these emitters are unknown and the metabolism is dependent on the organ species and may be influenced by many factors such as blood flow rate and fluid components present. In this paper, the washout rate of 11C activity implanted by injecting energetic 11C beams into thigh muscle of a rear leg of a rabbit is presented. The washout was found to consist of two components, the shorter one was about 4.2 ± 1.1 min and the longer one ranged from 91 to 124 min. About one third of the implanted β+ activity can be used for imaging and the rest was washed out of the target area.

https://iopscience.iop.org/article/10.1088/0031-9155/48/7/305/pdf

Washout studies of 11C in rabbit thigh muscle implanted by secondary beams of HIMAC

https://escholarship.org/content/qt8rs1160r/qt8rs1160r.pdf?t=p0fum6

A.R. Smith

Papers

Radioactive fragmentation of N7+ ion beam observed in a beryllium target