Radio-Guided Surgery with a New-Generation β-Probe for Radiolabeled Somatostatin Analog, in Patients with Small Intestinal Neuroendocrine Tumors.

Background: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs.

Objective: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a β-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives.

First-in-human validation of a DROP-IN β-probe for robotic radioguided surgery: defining optimal signal-to-background discrimination algorithm.

Purpose: In radioguided surgery (RGS), radiopharmaceuticals are used to generate preoperative roadmaps (e.g., PET/CT) and to facilitate intraoperative tracing of tracer avid lesions.

Experimental validation of an innovative approach in biokinetics study for personalised dosimetry of molecular radiation therapy treatments.

One of today's main challenges in molecular radiation therapy is to assess an individual dosimetry that allows treatment to be tailored to the specific patient, in accordance with the current paradigm of 'personalized medicine'. The evaluation of the absorbed doses for tumor and organs at risk in molecular radiotherapy is typically based on MIRD schema acquiring few experimental points for the assessement of biokinetic parameters. WIDMApp, the wearable individual dose monitoring apparatus, is an innovative approach for internal dosimetry based on a wearable radiation detecting system for individual biokinetics sampling, a Monte Carlo simulation for particle interaction, and an unfolding algorithm for data analysis and integrated activity determination at organ level.

Radioguided surgery with β decay: A feasibility study in cervical cancer.

Purpose: Radioguided surgery (RGS) is a technique that helps the surgeon to achieve a tumour resection as complete as possible, by means of the intraoperative detection of particles emitted by a radiotracer that bounds to tumoural cells. This study aimed to investigate the applicability of β-RGS for tumour resection and margin assessment in cervical cancer patients preoperatively injected with [F]FDG, by means of Monte Carlo simulations.

Methods: Patients were retrospectively included if they had a recurrent or persistent cervical cancer, underwent preoperative PET/CT to exclude distant metastases and received radical surgery.

Characterization and optimization of a β detector for F radio-guided surgery.

Radio-Guided Surgery (RGS) is a nuclear medicine technique to support the surgeon during surgery towards a complete tumor resection. It is based on intraoperative detection of radiation emitted by a radio-pharmaceutical that bounds selectively to tumoral cells. In the past years, an approach that exploits β emitting radiotracers has been pursued to overtake some limitations of the traditional RGS based on γ emission.

Theoretical Modeling for the Thermal Stability of Solid Targets in a Positron-Driven Muon Collider.

A future multi-TeV muon collider requires new ideas to tackle the problems of muon production, accumulation and acceleration. In the Low EMittance Muon Accelerator concept a 45 GeV positron beam, stored in an accumulation ring with high energy acceptance and low angular divergence, is extracted and driven to a target system in order to produce muon pairs near the kinematic threshold. However, this scheme requires an intensity of the impinging positron beam so high that the energy dissipation and the target maintenance are crucial aspects to be investigated.

Technical note: A wearable radiation measurement system for collection of patient-specific time-activity data in radiopharmaceutical therapy: system design and Monte Carlo simulation results.

Purpose: A high level of personalization in Molecular Radiotherapy (MRT) could bring advantages in terms of treatment effectiveness and toxicity reduction. Individual organ-level dosimetry is crucial to describe the radiopharmaceutical biodistribution expressed by the patient, to estimate absorbed doses to normal organs and target tissue(s). This paper presents a proof-of-concept Monte Carlo simulation study of "WIDMApp" (Wearable Individual Dose Monitoring Apparatus), a multi-channel radiation detector and data processing system for in vivo patient measurement and collection of radiopharmaceutical biokinetic data (i.

Beta radioguided surgery: towards routine implementation?

In locally or locally advanced solid tumors, surgery still remains a fundamental treatment method. However, conservative resection is associated with high collateral damage and functional limitations of the patient. Furthermore, the presence of residual tumor tissue following conservative surgical treatment is currently a common cause of locally recurrent cancer or of distant metastases.

First Results of β-Radioguided Surgery in Small Intestine Neuroendocrine Tumors with Y-DOTATOC.

In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with β-radioisotopes is a novel approach focused on developing a new probe that, detecting electrons and operating with low background, provides a clearer delineation of the lesions with low radiation exposition for surgeons. As a first step to validate this procedure, specimens of tumors expressing somatostatin receptors, as small intestine neuroendocrine tumor (SI-NET), were tested.

Y-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 β- emitting radioimmunoconjugate (Y-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.

Feasibility study on the use of CMOS sensors as detectors in radioguided surgery with β- emitters.

Radioguided surgery (RGS) is a medical practice which thanks to a radiopharmaceutical tracer and a probe allows the surgeon to identify tumor residuals up to a millimetric resolution in real-time. The employment of β emitters, instead of γ or β, reduces background from healthy tissues, administered activity to the patient, and medical exposure. In a previous work the possibility of using a CMOS Imager (Aptina MT9V011), initially designed for visible light imaging, to detect β from Y or Sr sources has been established.

A DROP-IN beta probe for robot-assisted Ga-PSMA radioguided surgery: first ex vivo technology evaluation using prostate cancer specimens.

Background: Recently, a flexible DROP-IN gamma-probe was introduced for robot-assisted radioguided surgery, using traditional low-energy SPECT-isotopes. In parallel, a novel approach to achieve sensitive radioguidance using beta-emitting PET isotopes has been proposed. Integration of these two concepts would allow to exploit the use of PET tracers during robot-assisted tumor-receptor-targeted.

Tumor-non-tumor discrimination by a β detector for Radio Guided Surgery on ex-vivo neuroendocrine tumors samples.

This paper provides a first insight of the potential of the β Radio Guided Surgery (β-RGS) in a complex surgical environment like the abdomen, where multiple sources of background concur to the signal at the tumor site. This case is well reproduced by ex-vivo samples of 90-marked Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP NET) in the bowel. These specimens indeed include at least three wide independent sources of background associated to three anatomical districts (mesentery, intestine, mucose).

Radioguided surgery with β radiation in pancreatic Neuroendocrine Tumors: a feasibility study.

The possibility to use β decaying isotopes for radioguided surgery (RGS) has been recently proposed, and first promising tests on ex-vivo samples of Meningioma and intestinal Neuroendocrine Tumor (NET) have been published. This paper reports a study of the uptake of Ga-DOTATOC in pancreatic NETs (pNETs) in order to assess the feasibility of a new RGS approach using Y-DOTATOC. Tumor and healthy pancreas uptakes were estimated from Ga-DOTATOC PET/CT scans of 30 patients with pNETs.

Characterisation of a β detector on positron emitters for medical applications.

Purpose: Radio Guided Surgery (RGS) is a technique that helps the surgeon to achieve an as complete as possible tumor resection, thanks to the intraoperative detection of particles emitted by a radio tracer that bounds to tumoral cells. In the last years, a novel approach to this technique has been proposed that, exploiting β emitting radio tracers, overtakes some limitations of established γ-RGS. In this context, a first prototype of an intraoperative β particle detector, based on a high light yield and low density organic scintillator, has been developed and characterised on pure β emitters, like Y.

The β radio-guided surgery: Method to estimate the minimum injectable activity from ex-vivo test.

Purpose: Radio-guided surgery with β decays is a novel technique under investigation. One of the main advantages is its capability to detect small (⩽0.1 ml) samples after injecting the patient with low activity of radiopharmaceutical.

Radioguided surgery with β radiation: a novel application with Ga.

Radio Guided Surgery is a technique helping the surgeon in the resection of tumors: a radiolabeled tracer is administered to the patient before surgery and then the surgeon evaluates the completeness of the resection with a handheld detector sensitive to emitted radiation. Established methods rely on γ emitting tracers coupled with γ detecting probes. The efficacy of this technique is however hindered by the high penetration of γ radiation, limiting its applicability to low background conditions.

Mass spectrometry characterization of DOTA-Nimotuzumab conjugate as precursor of an innovative β tracer suitable in radio-guided surgery.

The aim of the present work has been the mass spectrometry characterization of the Nimotuzumab (NIM) antibody chemically modified with the bifunctional chelating agent para-S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraaza cyclododecanetetraacetic acid (p-SCN-Bn-DOTA). The conjugate, upon labeling with the pure β-emitter Y could represent a promising candidate as radiotracer for an innovative radio-guided surgery (RGS) technique, developed and patented by researchers of our group, which uses a probe system for intraoperative detection of tumor residues exploiting the selective uptake of β-emitting tracers. The results reported in this study show that multiple DOTA molecules bind to lysine residues of both light and heavy chains of the antibody and, probably, some of them are linked to the variable region of antibody.

Secondary radiation measurements for particle therapy applications: charged particles produced by He and C ion beams in a PMMA target at large angle.

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.

Feasibility of beta-particle radioguided surgery for a variety of "nuclear medicine" radionuclides.

Purpose: Beta-particle radioguided tumor resection may potentially overcome the limitations of conventional gamma-ray guided surgery by eliminating, or at least minimizing, the confounding effect of counts contributed by activity in adjacent normal tissues. The current study evaluates the clinical feasibility of this approach for a variety of radionuclides. Nowadays, the only β radioisotope suited to radioguided surgery is Y.

Benchmarking Geant4 hadronic models for prompt-γ monitoring in carbon ion therapy.

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 C ion beam with a polymethyl methacrylate (PMMA) target.

Secondary radiation measurements for particle therapy applications: nuclear fragmentation produced by He ion beams in a PMMA target.

Nowadays there is a growing interest in particle therapy treatments exploiting light ion beams against tumors due to their enhanced relative biological effectiveness and high space selectivity. In particular promising results are obtained by the use of He projectiles. Unlike the treatments performed using protons, the beam ions can undergo a fragmentation process when interacting with the atomic nuclei in the patient body.

Secondary radiation measurements for particle therapy applications: prompt photons produced by He, C and O ion beams in a PMMA target.

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 (Z  >  1) 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.

Design of a new tracking device for on-line beam range monitor in carbon therapy.

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.