A novel figure of merit to investigate 68Ga PET/CT image quality based on patient weight and lesion size using Q.Clear reconstruction algorithm: A phantom study.

INTRODUCTION: Q.Clear is a Bayesian penalised-likelihood algorithm that uses a ß-value for positron emission tomography(PET)/computed tomography(CT) image reconstruction(IR). Our study proposes a novel figure of merit, named CRBV, to compare the Q.Clear performances using 68Ga PET/CT image with the ordered-subset-expectation-maximization(OSEM) algorithm and to identify the optimal ß-values for these images using two phantoms mimicking normal and overweight patients. METHODS: NEMA IQ phantom with or without a ring of water-filled plastic bags (NEMAstd and NEMAow, respectively) was acquired and reconstructed with OSEM and Q.Clear at various ß-values and minutes/bed position(min/bp). Contrast recovery(CR), background variability(BV) and CRBV were calculated. Highest CRBV values were used to identify optimal ß-value ranges. RESULTS: Q.Clear with 250 ≤ ß ≤ 800 improved CRBV compared to OSEM for all the investigated spheres and acquisition setups. Outside of this range, Q.Clear still outperformed OSEM with few exceptions depending on spheres diameters and phantoms(e.g.,ß-value = 1600 for diameters ≤ 17 mm using the NEMAow phantom). Regarding the CRBV performance for IR optimization, for the 4 min/bp NEMAstd IR, ß-values = 300 ÷ 350 allowed to simultaneously optimize all diameters(except for the 10 mm); for the NEMAow IR, ß-values = 350 ÷ 500 were needed for diameters > 20 mm, while ß-values = 200 ÷ 250 were selected for the remaining diameters. For the 2 min/bp, ß-value = 500 was suitable for diameters > 17 mm in both NEMAstd and NEMAow IR, while for smaller diameters ß-value = 200 and ß-values = 250 ÷ 350 were obtained for NEMAstd and NEMAow, respectively. CONCLUSION: Almost all tested ß-values of Q.Clear improved the CRBV compared to OSEM. In both phantoms, simulating normal and over-weight patients, optimal ß-values were found according to lesion sizes and investigated acquisition times.

A novel tool for predicting the dose distribution of non-sealed 188 Re (Rhenium) resin in non-melanoma skin cancers (NMSC) patients.

BACKGROUND: High-dose rate brachytherapy using a non-sealed 188 Rhenium resin (188 Re) is a recently approved treatment option for non-melanoma skin cancer (NMSC). The treatment goal is to deliver a personalized absorbed dose to the deepest point of neoplastic infiltration corresponding to the minimal target dose. The treatment consists of the application of a 188 Re-based resin over a plastic foil placed on the target skin surface. However, there is no treatment planning tool to assess the 188 Re activity needed for a personalized treatment. PURPOSE: The paper aims to present a novel Monte Carlo (MC)-based tool for 188 Re-based resin activity and dose calculation, experimentally validated using Gafchromic EBT3 films. METHODS: MC simulations were carried out using FLUKA modeling density and composition of 188 Re resin. The MC-based look up table (LUT) was incorporated in an ad hoc developed tool. The proposed tool allows the personalized calculation of treatment parameters (i.e., activity to be dispensed, the treatment duration, and dose volume histograms), according to the target dimension. The proposed tool was compared using Bland-Altman analysis to the previous calculation approaches conducted using VARSKIN in a retrospective cohort of 76 patients. The tool was validated in ad hoc experimental set ups using a stack of calibrated Gafchromic EBT3 films covered by a plastic film and exposed using a homogenous activity distribution of 188 Re eluate and a heterogeneous activity distribution of 188 Re resin mimic the patient treatment. RESULTS: The agreement between the proposed tool and VARSKIN was evaluated on the investigated cohort with median range of target area, target depth, and treatment time equal to 4.8 [1.0-60.1] cm2 , 1.1 [0.2-3.0] mm, and 70 [21-285] min, with a median range of target dose (Gy) of 23.5 [10-54.9]. The calculated minimal target doses, ranged from 1% to 10% for intermediate target depths (1.2 ± 0.7 mm), while showing significant differences in the estimation of superficial (maximal) target doses. The agreement between MC calculation and measurements at different plans in a stack of Gafchromic EBT3 films was within 10% for both the homogenous and heterogeneous activity distribution of 188 Re. Worst agreements were observed for absorbed doses lower than 0.3 Gy. CONCLUSIONS: Our results support the implementation of our MC-based tool in the practical routine for calculating the 188 Re resin activity and treatment parameters necessary for obtaining the prescribed minimal target dose.

A novel tool for motion-related dose inaccuracies reduction in 99mTc-MAA SPECT/CT images for SIRT planning.

INTRODUCTION: In Selective Internal Radiation Therapy (SIRT), 90Y is administered to primary/secondary hepatic lesions. An accurate pre-treatment planning using 99mTc-MAA SPECT/CT allows the assessment of its feasibility and of the activity to be injected. Unfortunately, SPECT/CT suffers from patient-specific respiratory motion which causes artifacts and absorbed dose inaccuracies. In this study, a data-driven solution was developed to correct the respiratory motion. METHODS: The tool realigns the barycenter of SPECT projection images and shifts them to obtain a fine registration with the attenuation map. The tool was validated using a modified dynamic phantom with several breathing patterns. We compared the absorbed dose distributions derived from uncorrected(Dm)/corrected(Dc) images with static ones(Ds) in terms of γ-passing rates, 210 Gy isodose volumes, dose-volume histograms and percentage differences of mean doses (i.e., ΔD¯m and ΔD¯c, respectively). The tool was applied to twelve SIRT patients and the Bland-Altman analysis was performed on mean doses. RESULTS: In the phantom study, the agreement between Dc and Ds was higher (γ-passing rates generally > 90%) than Dm and Ds. The isodose volumes in Dc were closer than Dm to Ds, with differences up to 10% and 30% respectively. A reduction from a median ΔD¯m = -19.3% to ΔD¯c = -0.9%, from ΔD¯m = -42.8% to ΔD¯c = -7.0% and from ΔD¯m = 1586% to ΔD¯c = 47.2% was observed in liver-, tumor- and lungs-like structures. The Bland-Altman analysis on patients showed variations (±50 Gy) and (±4 Gy) between D¯c and D¯m of tumor and lungs, respectively. CONCLUSION: The proposed tool allowed the correction of 99mTc-MAA SPECT/CT images, improving the accuracy of the absorbed dose distribution.

Alternative and New Radiopharmaceutical Agents for Lung Cancer.

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.

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

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.

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

PURPOSE: In recent years the use of 68Ga (t1/2 = 67.84 min, ß+: 88.88%) for the labelling of different PET radiopharmaceuticals has significantly increased. This work aims to evaluate the feasibility of the production of 68Ga via the 68Zn(p,n)68Ga 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 68Zn(NO3)2 in 0.2 N HNO3 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 67Ga through the68Zn(p,2n)67Ga reaction. The product's activity was measured using a calibrated activity meter and a High Purity Germanium gamma-ray detector. RESULTS: The saturation yield of68Ga amounts to (330 ±â€¯20) MBq/µA, corresponding to a produced activity of68Ga at the EOB of (4.3 ±â€¯0.3) GBq in a typical production run at 46 µA for 32 min. The radionuclidic purity of the68Ga 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 of68Ga by cyclotron irradiation of a liquid target, as a competitive alternative to the current production through the68Ge/68Ga generators.

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

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 [99mTc][TcO4]- ubiquitously employed for the production of 99mTc-radiopharmaceuticals in hospitals. These technologies make use almost exclusively of the nuclear reaction 100Mo(p,2n)99mTc 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 99Mo/99mTc 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.

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

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.

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

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.

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

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.

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

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.