In-room test results at CNAO of an innovative PT treatments online monitor (Dose Profiler)

The use of C, He and O ions as projectiles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of their enhanced relative biological effectiveness and oxygen enhancement ratio, when compared to the protons one. The advantages related to the incoming radiation improved efficacy are requiring an accurate online monitor of the dose release spatial distribution. Such monitor is necessary to prevent unwanted damage to the tissues surrounding the tumour that can arise, for example, due to morphological changes occurred in the patient during the treatment with respect to the initial CT scan. PT treatments with ions can be monitored by detecting the secondary radiation produced by the primary beam interactions with the patient body along the path towards the target volume. Charged fragments produced in the nuclear process of projectile fragmentation can be emitted at large angles with respect to the incoming beam direction and can be detected with high efficiency in a nearly background-free environment. The Dose Profiler (DP) detector, developed within the INSIDE project, is a scintillating fibre tracker that allows an online reconstruction and backtracking of such secondary charged fragments. The construction and preliminary in-room tests performed on the DP, carried out using the 12C ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution. The impact of the secondary fragments interactions with the patient body will be discussed in view of a clinical application. Furthermore, the results implications for a pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed

Scintillating fiber devices for particle therapy applications

Particle Therapy (PT) is a radiation therapy technique in which solid tumors are treated with charged ions and exploits the achievable highly localized dose delivery, allowing to spare healthy tissues and organs at risk. The development of a range monitoring technique to be used on-line, during the treatment, capable to reach millimetric precision is considered one of the important steps towards an optimization of the PT efficacy and of the treatment quality. To this aim, charged secondary particles produced in the nuclear interactions between the beam particles and the patient tissues can be exploited. Besides charged secondaries, also neutrons are produced in nuclear interactions. The secondary neutron component might cause an undesired and not negligible dose deposition far away from the tumor region, enhancing the risk of secondary malignant neoplasms that can develop even years after the treatment. An accurate neutron characterization (flux, energy and emission profile) is hence needed for a better evaluation of long-term complications. In this contribution two tracker detectors, both based on scintillating fibers, are presented. The first one, named Dose Profiler (DP), is planned to be used as a beam range monitor in PT treatments with heavy ion beams, exploiting the charged secondary fragments production. The DP is currently under development within the INSIDE (Innovative Solutions for In-beam DosimEtry in hadrontherapy) project. The second one is dedicated to the measurement of the fast and ultrafast neutron component produced in PT treatments, in the framework of the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project. Results of the first calibration tests performed at the Trento Protontherapy center and at CNAO (Italy) are reported, as well as simulation studies

Measurement of secondary particle production induced by particle therapy ion beams impinging on a PMMA target

Particle therapy is a technique that uses accelerated charged ions for cancer treatment and combines a high irradiation precision with a high biological effectiveness in killing tumor cells [1]. Informations about the secondary particles emitted in the interaction of an ion beam with the patient during a treatment can be of great interest in order to monitor the dose deposition. For this purpose an experiment at the HIT (Heidelberg Ion-Beam Therapy Center) beam facility has been performed in order to measure fluxes and emission profiles of secondary particles produced in the interaction of therapeutic beams with a PMMA target. In this contribution some preliminary results about the emission profiles and the energy spectra of the detected secondaries will be presente

Extended calibration range for prompt photon emission in ion beam irradiation

Monitoring the dose delivered during proton and carbon ion therapy is still a matter of research. Among the possible solutions, several exploit the measurement of the single photon emission from nuclear decays induced by the irradiation. To fully characterize such emission the detectors need development, since the energy spectrum spans the range above the MeV that is not traditionally used in medical applications. On the other hand, a deeper understanding of the reactions involving gamma production is needed in order to improve the physic models of Monte Carlo codes, relevant for an accurate prediction of the prompt-gamma energy spectrum.This paper describes a calibration technique tailored for the range of energy of interest and reanalyzes the data of the interaction of a 80MeV/u fully stripped carbon ion beam with a Poly-methyl methacrylate target. By adopting the FLUKA simulation with the appropriate calibration and resolution a significant improvement in the agreement between data and simulation is reported.Comment: 4 pages, 7 figures, Submitted to JINS

First Ex-Vivo Validation of a Radioguided Surgery Technique with beta- Radiation

Purpose: A radio-guided surgery technique with beta- -emitting radio-tracers was suggested to overcome the effect of the large penetration of gamma radiation. The feasibility studies in the case of brain tumors and abdominal neuro-endocrine tumors were based on simulations starting from PET images with several underlying assumptions. This paper reports, as proof-of-principle of this technique, an ex-vivo test on a meningioma patient. This test allowed to validate the whole chain, from the evaluation of the SUV of the tumor, to the assumptions on the bio-distribution and the signal detection. Methods: A patient affected by meningioma was administered 300 MBq of 90Y-DOTATOC. Several samples extracted from the meningioma and the nearby Dura Mater were analyzed with a beta- probe designed specifically for this radio-guided surgery technique. The observed signals were compared both with the evaluation from the histology and with the Monte Carlo simulation. Results: we obtained a large signal on the bulk tumor (105 cps) and a significant signal on residuals of $\sim$0.2 ml (28 cps). We also show that simulations predict correctly the observed yields and this allows us to estimate that the healthy tissues would return negligible signals (~1 cps). This test also demonstrated that the exposure of the medical staff is negligible and that among the biological wastes only urine has a significant activity. Conclusions: This proof-of-principle test on a patient assessed that the technique is feasible with negligible background to medical personnel and confirmed that the expectations obtained with Monte Carlo simulations starting from diagnostic PET images are correct.Comment: 17 pages, 4 Figs, Accepted by Physica Medic

Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

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 γ s, produced in the positron annihilation from β + 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 γ 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

Intraoperative probe detecting β− decays in brain tumour radio-guided surgery

Abstract Radio-guided surgery (RGS) is a technique to intraoperatively detect tumour remnants, favouring a radical resection. Exploiting β − emitting tracers provides a higher signal to background ratio compared to the established technique with γ radiation, allowing the extension of the RGS applicability range. We developed and tested a detector based on para-terphenyl scintillator with high sensitivity to low energy electrons and almost transparent to γ s to be used as intraoperative probe for RGS with β − emitting tracer. Portable read out electronics was customised to match the surgeon needs. This probe was used for preclinical test on specific phantoms and a test on "ex vivo" specimens from patients affected by meningioma showing very promising results for the application of this new technique on brain tumours. In this paper, the prototype of the intraoperative probe and the tests are discussed; then, the results on meningioma are used to make predictions on the performance of the probe detecting residuals of a more challenging and more interesting brain tumour: the glioma

Characterization of a detector for β− radio-guided surgery

This paper reports a new device for the radio-guided surgery technique exploiting β− emitters. A specific intraoperative β− detecting probe based on a low-density organic crystal, the diphenylbutadiene-doped para-therphenyl, coupled by optical fibres to a photomultiplier, was developed. A portable readout electronics was designed to provide the surgeons with multi real-time feedback. The aspects related to the applicability of the device, in particular the perception of the spatial resolution of the probe and the comprehension time necessary to the operator to interpret the system response were investigated. Preliminary promising results support the possibility of using this innovative probe in cancer surgery

90Y-DOTA-nimotuzumab: synthesis of a promising β⁻ radiopharmaceutical

BACKGROUND: Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab with yttrium-90, in order to provide a beta- emitting radioimmunoconjugate (90Y-DOTA-nimotuzumab) potentially useful to assess the feasibility of a new radio-guided surgery approach.METHODS: The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50 fold excess of DOTA and then labelled with 90Y3+. The 90Y-DOTA-nimotuzumab preparation was optimized considering several parameters such as pH, temperature and reaction volume. Moreover, the 90Y-DOTA-nimotuzumab stability was evaluated in human plasma.RESULTS: The radioimmunoconjugate 90Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than 96%, and showed a good stability at 20°C as well as at 37°C in human plasma.CONCLUSIONS: The optimized conditions for a mild and easy preparation of 90Y-DOTA-nimotuzumab joined to a promising stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic radiopharmaceutical for beta- radio-guided surgery