Manufacturing of Radiopharmaceutical Isotopes through the LINAC 7 Accelerator for Biomedical Applications

MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 1 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS Victor Etxebarria1, Jorge Feuchtwanger1,2, Joaquín Portilla1, Josu Jugo1, Iñigo Arredondo1, Inari Badillo1, Estibalitz Asua1, Rafael Enparantza3, Iratxe Ariz3, Unai Etxebeste4 y Iñaki Hernandez4 1 IZPILab-Beam Laboratory. UPV/EHU. Facultad de Ciencia y Tecnología. Barrio Sarriena s/n - 48940 Leioa (España). 2 Ikerbasque. Basque Foundation for Science. Plaza Euskadi 5 - 48009 Bilbao (España). 3 TEKNIKER. Basque Research and Technology Alliance (BRTA). Iñaki Goenaga 5 - 20600 Eibar (España). 4 Egile S.L. Poligono Industrial Kurutz-gain 12-13, 20850 Mendaro (España). Received: 03/dec/2021 • Reviewing: 05/dec/2021 • Accepted: 02/mar/2022 • DOI: https://doi.org/10.6036/10466 TO CITE ARTICLE: GOMEZ-MARQUEZ, Diego Armando, LEDESMA-OROZCO, Elias Rigoberto, HINO, Ryutaro et al. IDENTIFICATION OF PARAMETERS FOR CHARACTERIZATION AT HIGH-TEMPERATURE OF 38MnVS6 STEEL USED IN HOT FORGING PROCESSES. DYNA, May 2022, vol. 97, n.3. DOI: https://doi.org/10.6036/10371 ABSTRACT: Linac 7 consists of a new generation linear proton accelerator completely designed and built at the Beam Laboratory (IZPILabBeam Laboratory) of the University of the Basque Country UPV/EHU. One of the most important health applications conceived within the Linac 7 project is the production of pharmaceuticals of various species, locally around large clinical centers. Currently, medical radioisotopes are manufactured externally to hospitals and involve the use of distant, expensive and complex infrastructures. This results in long transports, production of large doses of radioisotopes that decay rapidly over the several hours of transport, and also usually only elements with sufficient half-life for use as appropriate pharmaceuticals can be used, with no other options. Our compact Linac 7 linear accelerator allows the manufacture of multiple types of radioisotopes locally and tailored to the corresponding biomedical needs, including specific doses of pharmaceuticals for patients, on demand of the medical staff in our hospitals. Keywords: Particle accelerators, radiopharmacy, nuclear medicine RESUMEN: Linac 7 consiste en un acelerador lineal de protones de nueva generación completamente diseñado y construido en el Laboratorio de Haces de Partículas (IZPILab-Beam Laboratory) de la Universidad del Pais Vasco UPV/EHU. Una de las aplicaciones sanitarias más importantes concebidas dentro de dicho proyecto Linac 7 es la producción de fármacos de diversas especies, localmente en torno a grandes centros clínicos. Actualmente los radioisótopos médicos se fabrican externamente a los hospitales e implican uso de infraestructuras lejanas, caras y complejas. Ello da lugar a transportes largos, producciones de grandes dosis de radioisótopos que decaen rápidamente en las varias horas del transporte y además suelen poderse utilizar únicamente elementos de vida media suficiente para su uso como fármacos apropiados, sin otro tipo de opciones. Nuestro acelerador lineal compacto Linac 7 permite fabricación de múltiples tipos de radioisótopos localmente y a medida de las correspondientes necesidades biomédicas, incluyendo dosis específicas de fármacos para pacientes, a demanda del personal medico en nuestros hospitales. Palabras clave: Aceleradores de partículas, radiofarmacia, medicina nuclear FUNDING Basque Government, Department of Economic Development, Sustainability and Environment: Technologies for the development of compact particle accelerators LINAC7 KK-2018/00020. 1. - INTRODUCTION Nuclear Medicine can benefit from multiple types of radioisotopes that have been generated in the last decades for various medical uses such as therapy or diagnosis by computerized imaging. The oldest technique for computerized imaging using radioisotopes is called SPECT (Single Photon Emission Computer Tomography), using the isotope Technetium-99m 99mTc, which emits photons (gamma rays), and by means of a camera sensitive to these photons, which rotates around the patient capturing complete images that a computer classifies into sections of the whole tomography. The production of 99mTc has been performed for decades in nuclear reactors using Molybdenum-99 decay and in the last decade by means of proton accelerators that the IAEA (International Atomic Energy Agency) proposes to use [1]. The most useful medical diagnostic visualization technique is PET (Positron Emission Tomography), which, although it is still used somewhat less than the old SPECT, is gaining many improvements and is being used much more widely in medicine, given that the MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 2 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 image obtained generates better resolution and its interest has expanded enormously in recent years to different specializations of nuclear medicine. New PET imaging using various radiopharmaceuticals is therefore a field of extraordinary importance research for biomedicine [2]. The main application of our Linac 7 project is the production of radiopharmaceuticals for the PET diagnostic technique using positron emitters. Linac 7 is capable of compact, local, on-the-spot and on-demand production of several of these isotopes. The great advantage is the production of immediate doses for the patient in the hospital, without the need to generate large quantities, without requiring high radioactive activity and the possibility of using various types of isotopes with different half-lives, useful for imaging a variety of medical diagnoses. The use of Linac 7, being a compact accelerator, is a much more agile, economical and versatile possibility for the manufacture of radiopharmaceuticals with high biomedical interest. 2.- LINAC 7 COMPACT BASES Linac 7 is a project that incorporates a number of novel elements that, concatenated together, give rise to the global compact accelerator, which acts as a generator and accelerator of proton beams up to low energies (7 MeV). The project is still under development for multiple applications at the Particle Beam Laboratory of the University of the Basque Country UPV/EHU (IZPILabBeam Laboratory). Although the purpose of this article is to describe the most important medical application conceived in the project, in this section we will briefly show some of the basic elements of Linac 7, in order to make the article self-contained. 2.1.- PROTON GENERATION AND EXTRACTION Linac 7 is based on a new source for proton generation and compact particle beam extraction, developed at IZPILab-Beam Laboratory UPV/EHU [3, 4]. Figure 1 shows the ion source and the Low Energy Beam Transport (LEBT). The ion source is of the ECR (Electron Cyclotron Resonance) type. The source consists of a cylindrical cavity whose dimensions are such that it resonates at 3 GHz, the frequency of the microwaves injected into it to supply the power. Surrounding the chamber there is a series of permanent magnets that generate an axial magnetic field along the length of the chamber. The magnitude of the field is designed to be the same as that required for the free electrons to resonate at 3 GHz, thus maximizing the transfer of microwave energy introduced to the free electrons. Fig. 1. Initial structure of Linac 7, including the proton generation source, beam extraction and low energy beam transport (LEBT). Hydrogen gas is injected into the chamber at a controlled flow rate, and these energized free electrons upon impact with the H2 molecules, break them apart and ionize them, generating new free electrons and protons (H+), thus transforming the gas into plasma. Everything described above is electrically isolated from the rest of the structure by means of an alumina insulator (the white component in the central part of Figure 1 left image) and the dark red insulators seen in the lower left part of the same Figure 1. In this way, the plasma chamber can be brought up to a voltage of 30 kV, which is used to accelerate and extract the protons generated inside the chamber. In the grounded part of the structure, just to the right side of the chamber, there is an electrostatic lens composed of three parallel electrodes, the two ends electrically grounded and the central one at 15 kV, which give a first focus to the extracted proton beam. MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 3 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 What is seen in the right image of Figure 1 is the LEBT, in which two solenoids are used as magnetic lenses to transform the divergent beam leaving the source first into a parallel and then into a convergent beam entering the RF quadrupole. The LEBT also provides the vacuum to the entire system and houses the beam diagnostics that will be briefly described in the next section. 2.2.- PROTON BEAM DIAGNOSTICS As mentioned above, the central part of the LEBT, illustrated on the right side of Figure 1, contains the devices used to characterize the proton beam generated and extracted at the source. For beam characterization, Linac 7 incorporates two main diagnostics that can be inserted to intercept the beam, which we will describe briefly below. The first one is a Faraday cup, a diagnostic that gives a measure of the total beam current reaching that point. A schematic of the Faraday cup, which consists of a graphite cylinder with a conical opening, can be seen in Figure 2. This piece is electrically insulated so that when the beam hits it, the electric charges can only be diverted to ground through a galvanometer, thus allowing the beam current to be quantified. The galvanometer is connected to the gold connector on the upper left side of Figure 2. The connector on the right side is connected to a metal ring, also electrically insulated, at the entrance of the beam to the cup, which is polarized at 50 V to capture the secondary electrons that may be generated by the impact of the beam with the diagnostic. Fig. 2. Faraday cup for proton beam current measurement MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 4 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 Fig. 3. Pepper pot diagnostics to measure both proton beam shape and proton beam emittance The second diagnostic that Linac 7 includes in the LEBT area is what is known as a Pepper pot (internationally so called because it is based on a perforated plate that resembles a pepper pot), whose function is to determine both the shape and the emittance of the beam. A diagram of this diagnostic can be seen in Figure 3, which consists of a thin steel plate with a series of 0.5 mm diameter holes forming a square mesh with a center-to-center 2 mm spacing. Upon impact of the beam against this plate, most of the beam is intercepted and only where it coincides with the holes do the protons pass through, generating a series of subbeams. These subbeams continue their flight until they impact with a screen of phosphorescent material of type P-43 that converts the proton impacts into light. The image generated on the phosphorescent screen is reflected onto a 45° mirror so that the image can be captured by a low-light CCD camera. The beam profile is obtained directly, and the emittance is calculated from the position of the light spots generated on the screen. 2.3.- RADIO FRECUENCY QUADRUPOLE (RFQ) FOR PROTON ACCELERATION Linac 7 is conceived to inject energy into the proton beam with a series of resonant Radio Frequency cavities that accelerate the protons from the source output energy of 30 keV to the desired final energy of 7 MeV. For this project, this will be done in two stages: first from 30 keV to 5 MeV using a new generation Radio Frequency quadrupole and finally from 5 MeV to 7 MeV using a Drift Tube Linac linear accelerator (DTL). Fig. 4. Interior of the new generation compact radiofrequency quadrupole designed at IZPILab-Beam Laboratory UPV/EHU MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 5 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 The radiofrequency quadrupole is a special type of radiofrequency resonant cavity, which is subdivided into 4 lobes separated by vanes that interconnect in the center, as can be seen in Figure 4. The tips of the vanes are not smooth, but have a sinusoidal shape modulation which is what achieves the acceleration of the particles. The modulation of the vanes that face each other is the same, while between the vanes that are orthogonal, the modulations are out of phase so that the minimum modulation in one vane coincides with the maximum modulation of the other vane. The electromagnetic wave inside the cavity generates an electrical voltage difference between the tips of the vanes. Facing vanes have the same polarity to each other, and orthogonal vanes have the opposite polarity. As the polarity of the wave varies from positive to negative within the cavity, the polarity of the vanes varies as well. The magnitude of the field depends on the distance between vanes. To achieve acceleration, the wavelength of the modulation grows along the beam direction, and always equals the product of the wavelength of the RF feed multiplied by the velocity of the particles divided by the speed of light in vacuum. In this way it is achieved that the particles at all times are between the two vanes with the minimum separation, when the electric field between this is adequate to accelerate, and thanks to the dephasing with the orthogonal vanes at the minimum of the field that would tend to slow them down. Therefore, along their path, an accelerating field always acts on the particles. This accelerating structure is still in the design phase, but to validate the simulations and test the manufacturability of these structures in copper, what is known as a cold model (since it is not powered and therefore not heated) 500 mm long in oxygen-free copper C10100, about one third the length of the final RFQ, has been fabricated. This can be seen in Figure 5. Fig. 5. Radio frequency quadrupole (cold model) in IZPILab-Beam Laboratory for Linac 7 This model is not under vacuum, and is used to measure the shape of the electric field at the center, where the particles travel, the resonant frequency, and the effect of the tuning plungers that can be used to correct for small variations in resonant frequency and field flatness. In the photograph in Figure 5, six of the eight tuners can be seen, at one-quarter and three-quarters of the length. The DTL design will be started when the RFQ design is completed and fabrication begins. 3.- RADIOPHARMACEUTICALS FOR PET Positron emitters with short half-lives are of primary importance for medical diagnostics using PET. The isotopes that can be produced using Linac 7 include 18F, 15O, 13N and 11C. These radiopharmaceuticals emit positrons which, upon collision with electrons from the patient's body, generate photons that create an image that is computer-processed for viewing and diagnosis by medical personnel. By labeling the cells of the human body to be diagnosed with various types of isotopes, different images can be produced for multiple types of possible pathologies. Fluorine-18 is one of the most widely used isotopes currently used in many hospitals that can be manufactured externally since it has a short half-life but long enough (approximately 110 minutes) to be shipped to the medical center from outside. However, external MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 6 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 shipment requires the manufacture of many more doses of high radioactive activity that decay and deactivate during the hours involved in transport. Overall, therefore, the current external manufacture of the radiopharmaceutical requires excesses in terms of economy, energy, radioactivity and speed. The efficiency of these issues can be significantly improved by local manufacture of tailor-made pharmaceutical doses in the hospital itself. On the other hand, Oxygen, Nitrogen and Carbon are very important elements since they are constituents of the organic cells of the human body and can be used to label a wide variety of useful pharmaceutical compounds. However, the short half-life of their isotopes (15O: 2 minutes; 13N: 10 minutes; 11C: 20.4 minutes) requires local manufacture within the hospital itself, which implies in practice the real impossibility of their medical use unless this is manufactured immediately and without the need for transport. There is a great deal of interest in these other radiopharmaceuticals for PET, which are still rarely used in medicine. In particular, the great interest in 11C, which can replace ordinary 12C in any molecule in the human body, is very remarkable. Local fabrication of all types of PET radiopharmaceuticals by Linac 7 is therefore an important applicability for biomedicine. Thus, local and tailor-made fabrication of these promising isotopes by Linac 7 would allow their actual medical use. 4.- ACCELERATORS FOR THE PRODUCTION OF RADIOPHARMACEUTICALS The most common way to manufacture radiopharmaceuticals is to use nuclear reactors or particle accelerators [5]. The most common current form for this application is the use of cyclotrons [6], which have been in use for several decades. These devices are relatively heavy and bulky, and usually accelerate protons to energies of tens of MeV (Mega Electron-Volts) in medical applications. Their manufacturing and operating costs, maintenance and energy cost are too high for hospitals to make their use widespread. Linear accelerators, however, in particular a new compact generation such as Linac 7, have several advantages over traditional cyclotrons. Firstly, Linacs have much lower beam losses than cyclotrons, since the latter, by their very circular nature, are subjected at all times to centripetal Lorentz force that radiates photons tangentially so that the beam loses energy. Secondly, the Linac 7 is a much more compact, economical, lightweight accelerator with low energy and radiation protection requirements. These numerous advantages make Linac 7 an excellent alternative for producing radiopharmaceuticals in-house at low proton energy. There is a great deal of interest in Europe in the use of different particle accelerator options for the manufacture of medical radio isotopes. In particular, the European Commission promotes the ARIES Consortium (Accelerator Research and Innovation for European Science and Society), whose report [7], published on June 22, 2020, describes the current state of the art in the fabrication of medical radio isotopes with accelerators, and specifically expresses the scientific, medical and industrial interest in the development of new Linacs for PET. It is very remarkable in this important European report (pp: 24-28) the recommendations that the ARIES Consortium proposes for compact Linacs, very similar and fully compatible with the design of our own Linac 7. 5.- NUCLEAR REACTIONS FOR ISOTOPE PRODUCTION THROUGH ASCCELERATORS Isotopes useful for radiopharmaceuticals are produced by nuclear reactions that can be carried out in various ways [8]. In the case of particle accelerators, the idea is to accelerate a beam to a certain energy and collide it on a specific target. The measure of the interaction between the beam and the target nuclei is the so-called "cross section" of the collision, which is a parameter highly dependent on the beam energy. To design an accelerator usable for fabricating various PET isotopes, one must accelerate particles in useful ranges for the nuclear reactions one wishes to produce. We therefore took multiple known nuclear reactions for production of such important isotopes as Fluorine-18 [9], and IAEA documented databases for various medical radioisotopes [10, 11]. 5.1.- FLUORINE-18 The dominant PET isotope can be generated by multiple nuclear pathways. For maximum simplicity using Linac 7 we consider the 18O(p,n)18F reaction: 18O + p → 18F + n which involves the collision of the Linac 7 proton beam on the stable isotope of oxygen 18O. Figure 6 shows the cross section of such a reaction, which may well occur between 3 to 18 MeV (with a minimum cross section around 40 milli-barn) [9], sufficient for the Oxygen-18 nucleus target. MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 7 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 Fig. 6. Cross section for the 18O(p,n)18F nuclear reaction (Reference [9]). Figure 7 is taken from the IAEA database [10, 11], which yields a cross section for the 18O(p,n)18F reaction that also gives rise to proton energies on target between 3 and 18 MeV. Of great interest is also the maximum cross section of the Fluorine-18 fabrication by this reaction at low energy of around 5 MeV, perfectly in the energy range of the proton beam of the compact Linac 7 accelerator. Fig. 7. IAEA database: cross section measured 18O(p,n)18F (References [10, 11]) MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 8 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 5.2.- CARBON-11 The PET isotope of current major interest 11C together with 18F can also be generated by multiple nuclear pathways. By using simulation of different nuclear reactions with Monte Carlo methods, low energy pathways can be predicted. Figure 8 shows the simulation, using the SRNA-BNL code, of three types of nuclear reactions for 11C isotope generation [12]. Fig. 8. Simulation of the effective cross-section of different nuclear reactions for 11C fabrication (Reference [12] Brookhaven National Laboratory) For maximum simplicity by Linac 7 the minimum energy pathway is considered and we choose the reaction 14N(p,2p2n)11C: 14N + p → 11C + which involves the collision of the Linac 7 proton beam on the ordinary isotope of Nitrogen 14N, and obtaining the 11C isotope plus alpha particles, which can be easily stopped. Figure 9 shows the cross section plot for the 14N(p,2p2n)11C reaction using the IAEA database [10, 11]. It can be seen that around 7 MeV it produces excellent cross section for the considered nuclear reaction for PET 11C isotope production, so that the Linac 7 accelerator is perfectly conceived to adequately generate the new PET radiopharmaceutical of greatest current interest. Fig. 9. IAEA database: cross-section measured 14N(p,2p2n)11C (References [10, 11]) MANUFACTURING OF RADIOPHARMACEUTICAL ISOTOPES THROUGH THE LINAC 7 ACCELERATOR FOR BIOMEDICAL APPLICATIONS NUCLEONICS RESEARCH ARTICLE Victor Etxebarria, Jorge Feuchtwanger , Joaquín Portilla, Josu Jugo, Iñigo Arredondo, Inari Badillo, Estibalitz Asua, Rafael Enparantza, Iratxe Ariz, Unai Etxebeste y Iñaki Hernandez Particle accelerators Publicaciones DYNA SL -- c) Mazarredo nº 69 - 2º -- 48009-BILBAO (SPAIN) Tel +34 944 237 566 – www.revistadyna.com - email: [email protected] Pag. 9 / 12 ISSN: 0012-7361 eISSN: 1989-1490 / DYNA vol. 97, n. 3. DOI: https://doi.org/10.6036/10466 5.3.- NITROGEN-13 The important PET 13N isotope can also be generated by collision of the Linac 7 accelerator proton beam. Figure 10 shows the simulation using the SRNA-BNL code of two types of nuclear reactions for generation of the 13N isotope and one possibility of the 15O isotope [12]. Since we will keep on a low energy route, we will choose the 16O(p,2p2n)13N nuclear reaction: 16O + p → 13N + which involves the collision of the Linac 7 proton beam on the ordinary Oxygen 16O isotope, and the obtention of the 13N isotope plus alpha particles, which can be easily stopped. Fig. 10. Simulation of the cross-section of different nuclear reactions for 13N and 15O fabrication (Reference [12] Brookhaven National Laboratory). Figure 11 presents the cross section plot for the 16O(p,2p2n)13N reaction using the IAEA database [10, 11]. It is observed that around 8 MeV a maximum cross section occurs, but it perfectly allows the nuclear reaction around 7 MeV, and therefore the generation of the interesting new radiopharmaceutical isotope 13N is perfectly possible using the compact Linac 7 accelerator. Fig. 11. IAEA database: measured effective section 16O(p,2p2n)13N (References [10, 11])