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PurposeThe aim of this study was to synthesize and preclinically evaluate an 18F-PSMA positron emission tomography (PET) tracer. Prostate-specific membrane antigen (PSMA) specificity, biodistribution, and dosimetry in healthy and tumor-bearing mice were determined.MethodsSeveral conditions for the labeling of 18F-PSMA-11 via 18F-AlF-complexation were screened to study the influence of reaction temperature, peptide amount, ethanol volume, and reaction time. After synthesis optimization, biodistribution and dosimetry studies were performed in C57BL6 mice. For proof of PSMA-specificity, mice were implanted with PSMA-negative (PC3) and PSMA-positive (LNCaP) tumors in contralateral flanks. Static and dynamic microPET/computed tomography (CT) imaging was performed.ResultsQuantitative labeling yields could be achieved with >97 % radiochemical purity. The 18F-PSMA-11 uptake was more than 24-fold higher in PSMA-high LNCaP than in PSMA-low PC3 tumors (18.4 ± 3.3 %ID/g and 0.795 ± 0.260 %ID/g, respectively; p

Cyclotrons are one of the most important sources of radionuclides used in biomedical applications. The production of important radionuclides used in single-photon emission tomography techniques such as 123I, 67Ga, 201Tl, and 111In has been based for decades on cyclotrons, typically proton machines with an energy up to 30 MeV. The extraordinary growth of positron emission tomography (PET) has led to the development of new models and to the installation of numerous cyclotrons, typically accelerating protons in the energy range 10 to 20 MeV. These have been used for the production of the main PET radionuclides, namely, 11C, 13N, 15O, and above all, 18F. Recently, their use has been extended to the production of radiometals, like 68Ga, and even to the direct production of 99mTc. Moreover, cyclotrons are a valuable tool for research and for the education of new scientists. This critical review presents the main manufacturers and briefly discusses the characteristics of the models they currently offer on the market. [ABSTRACT FROM AUTHOR]

Despite its insufficient availability, Copper-67 is currently attracting much attention for its enormous potential for cancer therapy as theranostic radionuclide. This work aims to accurately measure the unexplored cross section 70Zn(p,x)67Cu in the energy range 45–70 MeV and to evaluate its potential advantages in the case of high-intensity proton beams provided by compact cyclotrons. Thin target foils of enriched 70Zn were manufactured by lamination at the INFN-LNL and irradiated at the ARRONAX facility using the stacked-foils method. A radiochemical procedure for the separation of Cu, Ga and Zn contaminants and the isolation of 67Cu from the irradiated material was developed. The efficiency of the chemical processing was determined for each foil by monitoring the activity of selected tracer radionuclides (61Cu, 66Ga and 69mZn) through γ-spectrometry. Experimental data of the 70Zn(p,x)67Cu, 64Cu, 67Ga, 66Ga, 69mZn, 65Zn cross sections were measured for the first time in the energy range 45–70 MeV and compared with the theoretical results obtained by using the TALYS code. The 67Cu production yield by using enriched 70Zn thick targets was compared with the results obtained by using 68Zn targets in the same irradiation conditions. [ABSTRACT FROM AUTHOR]

In the production of Positron Emission Tomography (PET) nuclides at a medical cyclotron facility Ar ( T = 109.34 m) is produced by the activation of air due to the neutron flux, according to the Ar( n, )Ar reaction. In this work, we describe a relatively inexpensive and readily reproducible methodology of air sampling that can be used for quantification of Ar during the routine production of PET nuclides. We report the results of an extensive measurement campaign in the cyclotron bunker and in the ducts of the ventilation system, before and after final filtering of the extracted air. Air Samples were analyzed using a gamma-ray spectrometry system equipped with HPGe detector, with proper correction of the efficiency calibration to account for the samples density. The results of measurement were then used to evaluate the Total Effective Dose (TED) to the population living in the surrounding areas, due to routine emissions in the operation of the cyclotron. The average Ar saturation yield per one liter of air emitted in the environment resulted to be (0.044 ± 0.007) Bq/(A ⋅ dm3). The maximum value of TED for the critical group of the population, even considering an overestimated workload, was less than 0.19 Sv/year, well below the level of radiological relevance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

With the ever-increasing number of cyclotron installations, and therefore of the maintenance personnel involved, the possibility of swift, ‘yes or no’ screening for internal contamination becomes a prized asset. The present work presents one such procedure, evolved from an approximate whole body counting technique in widespread use in emergency situations. A detailed analysis of possible pathways for contamination leads to pinpointing the nuclides of interest. Different calibration methods are applied, showing moderate variation among them. The minimum detectable activity of order 1000 Bq is determined. The method proves sensitive enough to exclude significant contamination, or to identify its presence instantly ‘on site’ to prompt further in-depth investigation. [ABSTRACT FROM PUBLISHER]

In this paper, radionuclidic impurities generated during the bombardment of an 20Ne gaseous matrix in the routine production of [18F]-fluorodopa were studied. 18F2 is produced by the GE PETtrace cyclotron capable of accelerating negative deuteron ions to an energy of 8.4 MeV. The materials of the target and of the Havar foil, the stable fluorine added as carrier and the natural isotope composition of neon may interact with deuterons and produce undesired radionuclides. To measure them, a sampling system has been realized. Samples of the irradiated gas have been measured by gamma-ray spectrometry. The results show how the radionuclidic purity obtained is very high after a short time from the end of bombardment (EOB). [ABSTRACT FROM AUTHOR]

MiRNAs are single stranded RNAs of 18-22 nucleotides. They are promising diagnostic and prognostic markers for several pathologies including tumors, neurodegenerative, cardiovascular and autoimmune diseases. In the present work the development and characterization of anti-miRNA radiolabeled probes based on peptide nucleic acids (PNAs) for potential non-invasive molecular imaging in vivo of giant cell arteritis are described. MiR-146a and miR-146b-5p were selected as targets because they have been found up-regulated in this disease. Anti-miR and scramble PNAs were synthesized and linked to carboxyfluorescein or DOTA. DOTA-anti-miR PNAs were then labelled with copper-64 (64Cu) to function as non-invasive molecular imaging tools. The affinity of the probes for the targets was assessed in vitro by circular dichroism and melting temperature. Differential uptake of fluorescein and 64Cu labeled anti-miRNA probes was tested on BCPAP and A549 cell lines, expressing different levels of miR-146a and -146b-5p. The experiments showed that the anti-miR-146a PNAs were more effective than the anti-miR-146b-5p PNAs. Anti-miR-146a PNAs could bind both miR-146a and miR-146b-5p. The uptake of fluorescein and 64Cu labeled anti-miR-146a PNAs was higher than that of the negative control scramble PNAs in miRNA expressing cells in vitro. 64Cu-anti-miR-146a PNAs might be further investigated for non-invasive PET imaging of miR-146 overexpressing diseases. [ABSTRACT FROM AUTHOR]

Technetium-99m (99mTc) is the most used radionuclide worldwide in nuclear medicine for diagnostic imaging procedures. 99mTc is typically extracted from portable generators containing 99Mo, which is produced normally in nuclear reactors as a fission product of highly enriched Uranium material. Due to unexpected outages or planned and unplanned reactor shutdown, significant 99mTc shortages appeared as a problem since 2008 The alternative cyclotron-based approach through the 100Mo(p,2n)99mTc reaction is considered one of the most promising routes for direct 99mTc production in order to mitigate potential 99Mo shortages. The design and manufacturing of appropriate cyclotron targets for the production of significant amounts of a radiopharmaceutical for medical use is a technological challenge. In this work, a novel solid target preparation method was developed, including sputter deposition of a dense, adherent, and non-oxidized Mo target material onto a complex backing plate. The latter included either chemically resistant sapphire or synthetic diamond brazed in vacuum conditions to copper. The target thermo-mechanical stability tests were performed under 15.6 MeV proton energy and different beam intensities, up to the maximum provided by the available GE Healthcare (Chicago, IL, USA) PET trace medical cyclotron. The targets resisted proton beam currents up to 60 µA (corresponding to a heat power density of about 1 kW/cm2) without damage or Mo deposited layer delamination. The chemical stability of the proposed backing materials was proven by gamma-spectroscopy analysis of the solution obtained after the standard dissolution procedure of irradiated targets in H2O2. [ABSTRACT FROM AUTHOR]