L. Piersanti

Toward Radioguided Surgery with β− Decays: Uptake of a Somatostatin Analogue, DOTATOC, in Meningioma and High-Grade Glioma

A novel radioguided surgery (RGS) technique for cerebral tumors using β− radiation is being developed. Checking for a radiotracer that can deliver a β− emitter to the tumor is a fundamental step in the deployment of such a technique. This paper reports a study of the uptake of 90Y-DOTATOC in meningiomas and high-grade gliomas (HGGs) and a feasibility study of the RGS technique in these types of tumor. Estimates were performed assuming the use of a β− probe under development with a sensitive area 2.55 mm in radius to detect 0.1-mL residuals. Methods: Uptake and background from healthy tissues were estimated on 68Ga-DOTATOC PET scans of 11 meningioma patients and 12 HGG patients. A dedicated statistical analysis of the DICOM images was developed and validated. The feasibility study was performed using full simulation of emission and detection of the radiation, accounting for the measured uptake and background rate. Results: All meningioma patients but one with an atypical extracranial tumor showed high uptake of DOTATOC. In terms of feasibility of the RGS technique, we estimated that by administering a 3 MBq/kg activity of radiotracer, the time needed to detect a 0.1-mL remnant with 5% false-negative and 1% false-positive rates is less than 1 s. Actually, to achieve a detection time of 1 s the required activities to administer were as low as 0.2–0.5 MBq/kg in many patients. In HGGs, the uptake was lower than in meningiomas, but the tumor-to-nontumor ratio was higher than 4, which implies that the tracer can still be effective for RGS. It was estimated that by administering 3 mBq/kg of radiotracer, the time needed to detect a 0.1-mL remnant is less than 6 s, with the exception of the only oligodendroma in the sample. Conclusion: Uptake of 90Y-DOTATOC in meningiomas was high in all studied patients. Uptake in HGGs was significantly worse than in meningiomas but was still acceptable for RGS, particularly if further research and development are done to improve the performance of the β− probe.

A novel radioguided surgery technique exploiting β − decays

The background induced by the high penetration power of the radiation is the main limiting factor of the current radio-guided surgery (RGS). To partially mitigate it, a RGS with β+-emitting radio-tracers has been suggested in literature. Here we propose the use of β−-emitting radio-tracers and β− probes and discuss the advantage of this method with respect to the previously explored ones: the electron low penetration power allows for simple and versatile probes and could extend RGS to tumours for which background originating from nearby healthy tissue makes probes less effective. We developed a β− probe prototype and studied its performances on phantoms. By means of a detailed simulation we have also extrapolated the results to estimate the performances in a realistic case of meningioma, pathology which is going to be our first in-vivo test case. A good sensitivity to residuals down to 0.1u2005ml can be reached within 1u2005s with an administered activity smaller than those for PET-scans thus making the radiation exposure to medical personnel negligible.

Study of the time and space distribution of beta+ emitters from 80 MeV/u carbon ion beam irradiation on PMMA

Abstract Proton and carbon ion therapy is an emerging technique used for the treatment of solid cancers. The monitoring of the dose delivered during such treatments and the on-line knowledge of the Bragg peak position is still a matter of research. A possible technique exploits the collinear 511 keV photons produced by positrons annihilation from β + emitters created by the beam. This paper reports rate measurements of the 511 keV photons emitted after the interactions of a 80 MeV / u fully stripped carbon ion beam at the Laboratori Nazionali del Sud (LNS) of INFN, with a poly-methyl methacrylate target. The time evolution of the β + rate was parametrized and the dominance of 11C emitters over the other species (13N, 15O, 14O) was observed, measuring the fraction of carbon ions activating β + emitters to be ( 10.3 ± 0.7 ) × 10 - 3 . The average depth in the PMMA of the positron annihilation from β + emitters was also measured, D β + = 5.3 ± 1.1 mm , to be compared to the expected Bragg peak depth D Bragg = 11.0 ± 0.5 mm obtained from simulations.

Performance of upstream interaction region detectors for the FIRST experiment at GSI

The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at GSI has been designed to study carbon fragmentation, measuring 12C double differential cross sections (∂2σ/∂θ∂E) for different beam energies between 100 and 1000 MeV/u. The experimental setup integrates newly designed detectors in the, so called, Interaction Region around the graphite target. The Interaction Region upstream detectors are a 250 μm thick scintillator and a drift chamber optimized for a precise measurement of the ions interaction time and position on the target. In this article we review the design of the upstream detectors along with the preliminary results of the data taking performed on August 2011 with 400 MeV/u fully stripped carbon ion beam at GSI. Detectors performances will be reviewed and compared to those obtained during preliminary tests, performed with 500 MeV electrons (at the BTF facility in the INFN Frascati Laboratories) and 80 MeV/u protons and carbon ions (at the INFN LNS Laboratories in Catania).

Secondary radiation measurements for particle therapy applications: prompt photons produced by

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Zu2009u2009>u2009u20091) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at [Formula: see text] and [Formula: see text] with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

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Charged particle therapy is a technique for cancer treatment that exploits hadron beams, mostly protons and carbon ions. A critical issue is the monitoring of the beam range so to check the correct dose deposition to the tumor and surrounding tissues. The design of a new tracking device for beam range real-time monitoring in pencil beam carbon ion therapy is presented. The proposed device tracks secondary charged particles produced by beam interactions in the patient tissue and exploits the correlation of the charged particle emission profile with the spatial dose deposition and the Bragg peak position. The detector, currently under construction, uses the information provided by 12 layers of scintillating fibers followed by a plastic scintillator and a pixelated Lutetium Fine Silicate (LFS) crystal calorimeter. An algorithm to account and correct for emission profile distortion due to charged secondaries absorption inside the patient tissue is also proposed. Finally detector reconstruction efficiency for charged particle emission profile is evaluated using a Monte Carlo simulation considering a quasi-realistic case of a non-homogenous phantom.

He,

The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages.

^{12}

Proton and carbon ion beams are used in the clinical practice for external radiotherapy treatments achieving, for selected indications, promising and superior clinical results with respect to x-ray based radiotherapy. Other ions, like [Formula: see text] have recently been considered as projectiles in particle therapy centres and might represent a good compromise between the linear energy transfer and the radiobiological effectiveness of [Formula: see text] ion and proton beams, allowing improved tumour control probability and minimising normal tissue complication probability. All the currently used p, [Formula: see text] and [Formula: see text] ion beams allow achieving sharp dose gradients on the boundary of the target volume, however the accurate dose delivery is sensitive to the patient positioning and to anatomical variations with respect to photon therapy. This requires beam range and/or dose release measurement during patient irradiation and therefore the development of dedicated monitoring techniques. All the proposed methods make use of the secondary radiation created by the beam interaction with the patient and, in particular, in the case of [Formula: see text] ion beams are also able to exploit the significant charged radiation component. Measurements performed to characterise the charged secondary radiation created by [Formula: see text] and [Formula: see text] particle therapy beams are reported. Charged secondary yields, energy spectra and emission profiles produced in a poly-methyl methacrylate (PMMA) target by [Formula: see text] and [Formula: see text] beams of different therapeutic energies were measured at 60° and 90° with respect to the primary beam direction. The secondary yield of protons produced along the primary beam path in a PMMA target was obtained. The energy spectra of charged secondaries were obtained from time-of-flight information, whereas the emission profiles were reconstructed exploiting tracking detector information. The obtained measurements are in agreement with results reported in the literature and suggests the feasibility of range monitoring based on charged secondary particle detection: the implications for particle therapy monitoring applications are also discussed.

C and

Purpose: The real‐time monitoring of the spread‐out Bragg peak would allow the planned dose delivered during treatment to be directly verified, but this poses a major challenge in modern ion beam therapy. A possible method to achieve this goal is to exploit the production of secondary particles by the nuclear reactions of the beam with the patient and correlate their emission profile to the planned target volume position. In this study, we present both the production rate and energy spectra of the prompt‐γ produced by the interactions of the 12C ion beam with a polymethyl methacrylate (PMMA) target. We also assess three different Monte Carlo models for prompt‐γ simulation based on our experimental data. Methods: The experiment was carried out at the GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany with a 220 MeV/u 12C ions beam impinging on a 5× 5× 20 cm3 polymethyl methacrylate beam stopping target, with the prompt‐γ being detected by a hexagonally‐shaped barium fluoride scintillator with a circumscribed radius of 5.4 cm and a length of 14 cm, placed at 60° and 90° with respect to the beam direction. Monte Carlo simulations were carried out with three different hadronic models from the geant4 code: binary ion cascade (BIC), quantum molecular dynamics (QMD), and Liege intranuclear cascade (INCL++). Results: An experimental prompt‐γ yield of 1.06 × 10−2 sr−1 was measured at 90° A good agreement was observed between the shapes of the experimental and simulated energy spectra, especially with the INCL++ physics list. The prompt‐γ yield obtained with this physics list was compatible with the measurement within 2σ, with a relative difference of 26% on average. BIC and QMD physics lists proved to be less accurate than INCL++, with the difference between the measured and simulated yields exceeding 100%. The differences between the three physics lists were ascribed to important discrepancies between the models of the physical processes producing prompt‐γ emissions. Conclusion: In conclusion, this study provides prompt‐γ yield values in agreement with previously published results for different carbon ions energies. This work demonstrates that the INCL++ physics list from geant4 is more accurate than BIC and QMD to reproduce prompt‐γ emission properties.

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Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back ??s, produced in the positron annihilation from ??+ emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt ??s) performed at different beam and energies that have a particular relevance for PT applications: 12C beam of 80 MeV/u at LNS, 12C beam 220 MeV/u at GSI, and 12C, 4He, 16O beams with energy in the 50?300 MeV/u range at HIT. Finally, a project for a multimodal dose-monitor device exploiting the prompt photons and charged particles emission will be presented.