Publications by authors named "Federico Zagni"

8 Publications

  • Page 1 of 1

Alternative and New Radiopharmaceutical Agents for Lung Cancer.

Curr Radiopharm 2020 ;13(3):185-194

Department of Metropolitan Nuclear Medicine, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Background: FDG PET/CT imaging has an established role in lung cancer (LC) management. Whilst it is a sensitive technique, FDG PET/CT has a limited specificity in the differentiation between LC and benign conditions and is not capable of defining LC heterogeneity since FDG uptake varies between histotypes.

Objective: To get an overview of new radiopharmaceuticals for the study of cancer biology features beyond glucose metabolism in LC.

Methods: A comprehensive literature review of PubMed/Medline was performed using a combination of the following keywords: "positron emission tomography", "lung neoplasms", "non-FDG", "radiopharmaceuticals", "tracers".

Results: Evidences suggest that proliferation markers, such as 18F-Fluorothymidine and 11CMethionine, improve LC staging and are useful in evaluating treatment response and progression free survival. 68Ga-DOTA-peptides are already routinely used in pulmonary neuroendocrine neoplasms (NENs) management and should be firstly performed in suspected NENs. 18F-Fluoromisonidazole and other radiopharmaceuticals show a promising impact on staging, prognosis assessment and therapy response in LC patients, by visualizing hypoxia and perfusion. Radiolabeled RGD-peptides, targeting angiogenesis, may have a role in LC staging, treatment outcome and therapy. PET radiopharmaceuticals tracing a specific oncogene/signal pathway, such as EGFR or ALK, are gaining interest especially for therapeutic implications. Other PET tracers, like 68Ga-PSMA-peptides or radiolabeled FAPIs, need more development in LC, though, they are promising for therapy purposes.

Conclusion: To date, the employment of most of the described tracers is limited to the experimental field, however, research development may offer innovative opportunities to improve LC staging, characterization, stratification and response assessment in an era of increased personalized therapy.
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January 2020

Production of Ga-68 with a General Electric PETtrace cyclotron by liquid target.

Phys Med 2018 Nov 25;55:116-126. Epub 2018 Oct 25.

Medical Physics Department, University Hospital, S. Orsola-Malpighi, Bologna, Italy.

Purpose: In recent years the use of Ga (t = 67.84 min, β: 88.88%) for the labelling of different PET radiopharmaceuticals has significantly increased. This work aims to evaluate the feasibility of the production of Ga via the Zn(p,n)Ga reaction by proton irradiation of an enriched zinc solution, using a biomedical cyclotron, in order to satisfy its increasing demand.

Methods: Irradiations of 1.7 Msolution of Zn(NO) in 0.2 N HNO were conducted with a GE PETtrace cyclotron using a slightly modified version of the liquid target used for the production of fluorine-18. The proton beam energy was degraded to 12 MeV, in order to minimize the production of Ga through theZn(p,2n)Ga reaction. The product's activity was measured using a calibrated activity meter and a High Purity Germanium gamma-ray detector.

Results: The saturation yield ofGa amounts to (330 ± 20) MBq/µA, corresponding to a produced activity ofGa at the EOB of (4.3 ± 0.3) GBq in a typical production run at 46 µA for 32 min. The radionuclidic purity of theGa in the final product, after the separation, is within the limits of the European Pharmacopoeia (>99.9%) up to 3 h after the EOB. Radiochemical separation up to a yield not lower than 75% was obtained using an automated purification module. The enriched material recovery efficiency resulted higher than 80-90%.

Conclusions: In summary, this approach provides clinically relevant amounts ofGa by cyclotron irradiation of a liquid target, as a competitive alternative to the current production through theGe/Ga generators.
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November 2018

In-house cyclotron production of high-purity Tc-99m and Tc-99m radiopharmaceuticals.

Appl Radiat Isot 2018 Sep 30;139:325-331. Epub 2018 May 30.

Legnaro Laboratories, Italian National Institute for Nuclear Physics (INFN), Legnaro, Padua, Italy; Department of Chemical and Pharmaceutical Sciences, University of Ferrara, Ferrara, Italy.

In the last years, the technology for producing the important medical radionuclide technetium-99m by cyclotrons has become sufficiently mature to justify its introduction as an alternative source of the starting precursor [Tc][TcO] ubiquitously employed for the production of Tc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction Mo(p,2n)Tc that allows direct production of Tc-99m. In this study, it is conjectured that this alternative production route will not replace the current supply chain based on the distribution of Mo/Tc generators, but could become a convenient emergency source of Tc-99m only for in-house hospitals equipped with a conventional, low-energy, medical cyclotron. On this ground, an outline of the essential steps that should be implemented for setting up a hospital radiopharmacy aimed at the occasional production of Tc-99m by a small cyclotron is discussed. These include (1) target production, (2) irradiation conditions, (3) separation/purification procedures, (4) terminal sterilization, (5) quality control, and (6) Mo-100 recovery. To address these issues, a comprehensive technology for cyclotron-production of Tc-99m, developed at the Legnaro National Laboratories of the Italian National Institute of Nuclear Physics (LNL-INFN), will be used as a reference example.
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September 2018

Modeling of a Cyclotron Target for the Production of 11C with Geant4.

Curr Radiopharm 2018 ;11(2):92-99

Medical Physics Unit, University Hospital "S. Orsola-Malpighi", Via Massarenti 9, 40138, Bologna, Italy.

Background: In medical cyclotron facilities, 11C is produced according to the 14N(p,α)11C reaction and widely employed in studies of prostate and brain cancers by Positron Emission Tomography. It is known from literature that the 11C-target assembly shows a reduction in efficiency during time, meaning a decrease of activity produced at the end of bombardment. This effect might depend on aspects which are still not completely known.

Objective: Possible causes of the loss of performance of the 11C-target assembly were addressed by Monte Carlo simulations.

Methods: Geant4 was used to model the 11C-target assembly of a GE PETtrace cyclotron. The physical and transport parameters to be used in the energy range of medical applications were extracted from literature data and 11C routine productions. The Monte Carlo assessment of 11C saturation yield was performed varying several parameters such as the proton energy and the angle of the target assembly with respect to the proton beam.

Results: The estimated 11C saturation yield is in agreement with IAEA data at the energy of interest, while it is about 35% greater than the experimental value. A more comprehensive modeling of the target system, including thermodynamic effect, is required. The energy absorbed in the inner layer of the target chamber was up to 46.5 J/mm2 under typical irradiation conditions.

Conclusion: This study shows that Geant4 is potentially a useful tool to design and optimize targetry for PET radionuclide productions. Tests to choose the Geant4 physics libraries should be performed before using this tool with different energies and materials.
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October 2018

Assessment of the neutron dose field around a biomedical cyclotron: FLUKA simulation and experimental measurements.

Phys Med 2016 Dec 3;32(12):1602-1608. Epub 2016 Dec 3.

Medical Physics Department, University Hospital "S. Orsola-Malpighi", Via Massarenti 9, 40138 Bologna, Italy.

In the planning of a new cyclotron facility, an accurate knowledge of the radiation field around the accelerator is fundamental for the design of shielding, the protection of workers, the general public and the environment. Monte Carlo simulations can be very useful in this process, and their use is constantly increasing. However, few data have been published so far as regards the proper validation of Monte Carlo simulation against experimental measurements, particularly in the energy range of biomedical cyclotrons. In this work a detailed model of an existing installation of a GE PETtrace 16.5MeV cyclotron was developed using FLUKA. An extensive measurement campaign of the neutron ambient dose equivalent H(10) in marked positions around the cyclotron was conducted using a neutron rem-counter probe and CR39 neutron detectors. Data from a previous measurement campaign performed by our group using TLDs were also re-evaluated. The FLUKA model was then validated by comparing the results of high-statistics simulations with experimental data. In 10 out of 12 measurement locations, FLUKA simulations were in agreement within uncertainties with all the three different sets of experimental data; in the remaining 2 positions, the agreement was with 2/3 of the measurements. Our work allows to quantitatively validate our FLUKA simulation setup and confirms that Monte Carlo technique can produce accurate results in the energy range of biomedical cyclotrons.
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December 2016

Radiation Protection Studies for Medical Particle Accelerators using Fluka Monte Carlo Code.

Radiat Prot Dosimetry 2017 Apr;173(1-3):185-191

Medical Physics Department, S. Orsola-Malpighi University Hospital, Via Massarenti 9, 40138 Bologna, Italy.

Radiation protection (RP) in the use of medical cyclotrons involves many aspects both in the routine use and for the decommissioning of a site. Guidelines for site planning and installation, as well as for RP assessment, are given in international documents; however, the latter typically offer analytic methods of calculation of shielding and materials activation, in approximate or idealised geometry set-ups. The availability of Monte Carlo (MC) codes with accurate up-to-date libraries for transport and interaction of neutrons and charged particles at energies below 250 MeV, together with the continuously increasing power of modern computers, makes the systematic use of simulations with realistic geometries possible, yielding equipment and site-specific evaluation of the source terms, shielding requirements and all quantities relevant to RP at the same time. In this work, the well-known FLUKA MC code was used to simulate different aspects of RP in the use of biomedical accelerators, particularly for the production of medical radioisotopes. In the context of the Young Professionals Award, held at the IRPA 14 conference, only a part of the complete work is presented. In particular, the simulation of the GE PETtrace cyclotron (16.5 MeV) installed at S. Orsola-Malpighi University Hospital evaluated the effective dose distribution around the equipment; the effective number of neutrons produced per incident proton and their spectral distribution; the activation of the structure of the cyclotron and the vault walls; the activation of the ambient air, in particular the production of 41Ar. The simulations were validated, in terms of physical and transport parameters to be used at the energy range of interest, through an extensive measurement campaign of the neutron environmental dose equivalent using a rem-counter and TLD dosemeters. The validated model was then used in the design and the licensing request of a new Positron Emission Tomography facility.
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April 2017

Attenuation correction for small animal PET images: a comparison of two methods.

Comput Math Methods Med 2013 16;2013:103476. Epub 2013 Apr 16.

Medical Physics Department, University Hospital S. Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy.

In order to extract quantitative parameters from PET images, several physical effects such as photon attenuation, scatter, and partial volume must be taken into account. The main objectives of this work were the evaluation of photon attenuation in small animals and the implementation of two attenuation correction methods based on X-rays CT and segmentation of emission images. The accuracy of the first method with respect to the beam hardening effect was investigated by using Monte Carlo simulations. Mouse- and rat-sized phantoms were acquired in order to evaluate attenuation correction in terms of counts increment and recovery of uniform activity concentration. Both methods were applied to mice and rat images acquired with several radiotracers such as(18)F-FDG, (11)C-acetate, (68)Ga-chloride, and (18)F-NaF. The accuracy of the proposed methods was evaluated in heart and tumour tissues using (18)F-FDG images and in liver, kidney, and spinal column tissues using (11)C-acetate, (68)Ga-chloride, and (18)F-NaF images, respectively. In vivo results from animal studies show that, except for bone scans, differences between the proposed methods were about 10% in rats and 3% in mice. In conclusion, both methods provide equivalent results; however, the segmentation-based approach has several advantages being less time consuming and simple to implement.
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December 2013

Molecular imaging of neuroblastoma progression in TH-MYCN transgenic mice.

Mol Imaging Biol 2013 Apr;15(2):194-202

Department of Nuclear Medicine, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.

Purpose: TH-MYCN transgenic mice represent a valuable preclinical model of neuroblastoma. Current methods to study tumor progression in these mice are inaccurate or invasive, limiting the potential of this murine model. The aim of our study was to assess the potential of small animal positron emission tomography (SA-PET) to study neuroblastoma progression in TH-MYCN mice.

Procedure: Serial SA-PET scans using the tracer 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) have been performed in TH-MYCN mice. Image analysis of tumor progression has been compared with ex vivo evaluation of tumor volumes and histological features.

Results: [(18)F]FDG-SA-PET allowed to detect early staged tumors in almost 100 % of TH-MYCN mice positive for disease. Image analysis of tumor evolution reflected the modifications of the tumor volume, histological features, and malignancy during disease progression. Image analysis of TH-MYCN mice undergoing chemotherapy treatment against neuroblastoma provided information on drug-induced alterations in tumor metabolic activity.

Conclusions: These data show for the first time that [(18)F]FDG-SA-PET is a useful tool to study neuroblastoma presence and progression in TH-MYCN transgenic mice.
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April 2013