Gaia Pupillo

Psychostimulant Effect of the Synthetic Cannabinoid JWH-018 and AKB48: Behavioral, Neurochemical, and Dopamine Transporter Scan Imaging Studies in Mice

JWH-018 and AKB48 are two synthetic cannabinoids (SCBs) belonging to different structural classes and illegally marketed as incense, herbal preparations, or chemical supply for theirs psychoactive cannabis-like effects. Clinical reports from emergency room reported psychomotor agitation as one of the most frequent effects in people assuming SCBs. This study aimed to investigate the psychostimulant properties of JWH-018 and AKB48 in male CD-1 mice and to compare their behavioral and biochemical effects with those caused by cocaine and amphetamine. In vivo studies showed that JWH-018 and AKB48, as cocaine and amphetamine, facilitated spontaneous locomotion in mice. These effects were prevented by CB1 receptor blockade and dopamine (DA) D1/5 and D2/3 receptors inhibition. SPECT-CT studies on dopamine transporter (DAT) revealed that, as cocaine and amphetamine, JWH-018 and AKB48 decreased the [123I]-FP-CIT binding in the mouse striatum. Conversely, in vitro competition binding studies revealed that, unlike cocaine and amphetamine, JWH-018 and AKB48 did not bind to mouse or human DAT. Moreover, microdialysis studies showed that the systemic administration of JWH-018, AKB48, cocaine, and amphetamine stimulated DA release in the nucleus accumbens (NAc) shell of freely moving mice. Finally, unlike amphetamine and cocaine, JWH-018 and AKB48 did not induce any changes on spontaneous [3H]-DA efflux from murine striatal synaptosomes. The present results suggest that SCBs facilitate striatal DA release possibly with different mechanisms than cocaine and amphetamine. Furthermore, they demonstrate, for the first time, that JWH-018 and AKB48 induce a psychostimulant effect in mice possibly by increasing NAc DA release. These data, according to clinical reports, outline the potential psychostimulant action of SCBs highlighting their possible danger to human health.

Experimental cross section evaluation for innovative 99Mo production via the (α,n) reaction on 96Zr target

The high-specific activity 99Mo accelerator-based production, via the (α,n) reaction on 96Zr-enriched target, has been investigated in the present work. The excitation function measurement has been performed in the energy range 8–34xa0MeV at the ARRONAX facility, using the well-known stacked foils technique on natural zirconium as target. A general good agreement in the cross section trend has been observed, once compared to former measurements. A different (i.e. higher) peak value and a shift of about 2xa0MeV towards larger energies have however been found. Assuming a fully enriched 96Zr target irradiated by an α-beam at suitable energy (Exa0=xa025xa0MeV), the 99Mo production yield has thus been estimated. At last the alternative production routes, based on the 96Zr(α,n)99Mo and 100Mo(p,x)99Mo/99mTc reactions, are compared.

A solvent-extraction module for cyclotron production of high-purity technetium-99m

The design and fabrication of a fully-automated, remotely controlled module for the extraction and purification of technetium-99m (Tc-99m), produced by proton bombardment of enriched Mo-100 molybdenum metallic targets in a low-energy medical cyclotron, is here described. After dissolution of the irradiated solid target in hydrogen peroxide, Tc-99m was obtained under the chemical form of 99mTcO4-, in high radionuclidic and radiochemical purity, by solvent extraction with methyl ethyl ketone (MEK). The extraction process was accomplished inside a glass column-shaped vial especially designed to allow for an easy automation of the whole procedure. Recovery yields were always >90% of the loaded activity. The final pertechnetate saline solution Na99mTcO4, purified using the automated module here described, is within the Pharmacopoeia quality control parameters and is therefore a valid alternative to generator-produced 99mTc. The resulting automated module is cost-effective and easily replicable for in-house production of high-purity Tc-99m by cyclotrons.

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.

Accelerator-based production of Mo-99: a comparison between the Mo-100(p,x) and Zr-96(alpha,n) reactions

AbstractnInnovative accelerator-based production routes for 99Mo (and 99mTc) have been studied, comparing the 100Mo(p,x)99Mo,99mTc and 96Zr(α,n)99Mo reactions, for which a new set of measurement has been made. Theoretical and experimental cross sections have been analysed and used to calculate 99Mo production yields and specific activity (SA), considering fully enriched and commercially available target materials. Results show that the low SA resulting from the p-based route forces the use of alternative generator systems, while the α-based reaction provides very high SA 99Mo but much lower yield. Benefits and drawbacks of direct 99mTc production via the 100Mo(p,2p) reaction are also discussed.

Abstract ID: 14 Montecarlo calculation of reaction cross sections for the production of innovative radionuclides

The production of innovative radionuclides in the context of theranostics is currently a topic of great interest. Various INFN projects are underway in search of new data and new techniques for radionuclides production. Among the possible channels under study, recent developments indicate 67Cu and 47Sc as good candidates competitive with more traditional nuclides, thanks to their application both for diagnostic and for therapy. INFN recently started two projects for the measurement of proton-induced reactions, considering the forthcoming use of the high-performance cyclotron installed at INFN-LNL (70u202fMeV maximum energy): COME in CSN3 (2016) and PASTA in CSN5 (Young Researchers grants 2016). The knowledge of reaction cross sections at low-intermediate energies is crucial in this context and, in parallel to the need of new measurements, it is important also to review the current situation in the reaction-model simulation of the production yields, by using the existing and available nuclear reaction codes. In particular the FLUKA code, based on the PEANUT (Pre-Equilibrium Approach to Nuclear Thermalisation) model, was used to calculate the production of residual nuclei in different experiments and is already validated with data. In this study we use FLUKA to calculate the reaction cross sections for the production of copper and scandium isotopes at the energy of interest for the LARAMED project (10–100u202fMeV). A comparison of the results obtained with dedicated codes (Talys and Empire) and with available experimental data is also given.

A new solvent-extraction module for a local routine production of technetium-99m by medical cyclotrons

s Listing Award-winning abstracts (selected for oral presentation)

Accelerator-based production of 99 Mo: a comparison between the 100 Mo(p,x) and 96 Zr(α,n) reactions

AbstractnInnovative accelerator-based production routes for 99Mo (and 99mTc) have been studied, comparing the 100Mo(p,x)99Mo,99mTc and 96Zr(α,n)99Mo reactions, for which a new set of measurement has been made. Theoretical and experimental cross sections have been analysed and used to calculate 99Mo production yields and specific activity (SA), considering fully enriched and commercially available target materials. Results show that the low SA resulting from the p-based route forces the use of alternative generator systems, while the α-based reaction provides very high SA 99Mo but much lower yield. Benefits and drawbacks of direct 99mTc production via the 100Mo(p,2p) reaction are also discussed.

Accelerator-based production of 99Mo: a comparison between the 100Mo(p,x) and 96Zr(α,n) reactions

AbstractnInnovative accelerator-based production routes for 99Mo (and 99mTc) have been studied, comparing the 100Mo(p,x)99Mo,99mTc and 96Zr(α,n)99Mo reactions, for which a new set of measurement has been made. Theoretical and experimental cross sections have been analysed and used to calculate 99Mo production yields and specific activity (SA), considering fully enriched and commercially available target materials. Results show that the low SA resulting from the p-based route forces the use of alternative generator systems, while the α-based reaction provides very high SA 99Mo but much lower yield. Benefits and drawbacks of direct 99mTc production via the 100Mo(p,2p) reaction are also discussed.