CERN-MEDICIS

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CERN-MEDICIS robot isotope production for medical research MEDICIS Robot.jpg
CERN-MEDICIS robot isotope production for medical research

CERN-MEDical Isotopes Collected from ISOLDE (MEDICIS) is a facility located in the Isotope Separator Online DEvice (ISOLDE) facility at CERN, designed to produce high-purity isotopes for developing the practice of patient diagnosis and treatment. The facility was initiated in 2010, with its first radioisotopes (terbium-155) produced on 12 December 2017. [1]

Contents

The target used to produce radioactive nuclei at the ISOLDE facility only absorbs 10% of the proton beam. [2] MEDICIS positions a second target behind the first, which is irradiated by the leftover 90% of the proton beam. The target is then moved to an off-line mass separation system and isotopes are extracted from the target. [3] These isotopes are implanted in metallic foil and can be delivered to research facilities and hospitals. [4]

MEDICIS is a nuclear class A laboratory and takes into account various radioprotection procedures to prevent irradiation and contamination. [5]

Background

An isotope of an element contains the same number of protons, but a different number of neutrons, giving it a different mass number than the element found on the periodic table. Isotopes with a large variation in nucleon number will decay into more stable nuclei, and are known as radionuclides or radioisotopes.

The field of nuclear medicine uses radioisotopes to diagnose and treat patients. The radiation and particles emitted by these radioisotopes can be used to weaken or destroy target cells, for example in the case of cancer. For diagnosis, a radioactive dose is given to a patient and its activity can be tracked to study the functionality of a target organ. The tracers used within this process are generally short-lived isotopes. [6]

Diagnostic radiopharmaceuticals are used to examine organ functionality, blood flow, bone growth and other diagnostic procedures.[ citation needed ] Radioisotopes needed for this procedure must emit gamma radiation with a high energy and short half-life, in order for it to escape the body and decay quickly. [7] There is currently a trend to use cyclotron-produced isotopes as they are becoming more widely available. [6]

Positron Emission of Fluorine-18 Positron Emission of Fluorine-18.png
Positron Emission of Fluorine-18

Positron emission tomography (PET) is an imaging technique, using radioisotopes also most often produced with a cyclotron. [8] They are injected into the patient, accumulating in the target tissue, and decays through positron emission. The positron annihilates with an electron nearby which results in the emission to two gamma rays (photons) in opposite directions. A PET camera detects these rays and can determine quantitative information about the target tissue. [9]

Therapeutic radiopharmaceuticals are used to destroy or weaken malfunctioning cells, using a radioisotope localised to a specific organ. This process is called radionuclide therapy (RNT), and uses heavy proton radioisotopes (located on the North-West area of the nuclide chart) that decay through beta or alpha emission. [10]

Facility and process

MEDICIS announcement of initial construction in 2013 MEDICIS Site.jpg
MEDICIS announcement of initial construction in 2013

The MEDICIS facility is located in the extension of building 179 at the CERN Meyrin site, next to the ISOLDE building. [11] The facility was established by CERN in 2010, along with contributions from the CERN Knowledge Transfer Fund, as well as receiving a European Commission Marie-Skłodowska-Curie training grant under the title MEDICIS-PROMED. [12] [13] The construction of the facility started in September 2013 and was completed in 2017. [14] [3]

ISOLDE directs a 1.4 GeV proton beam from the Proton Synchrotron Booster (PSB) onto a thick target, the material dependent on the desired produced isotopes. Only 10% of the proton beam used in the ISOLDE facility is absorbed by the target, with the rest otherwise hitting the beam dump. [15] MEDICIS uses these wasted protons to irradiate a second target, which produces specific isotopes, placed behind each of ISOLDE's target stations, the High Resolution Separator (HRS) and the General Purpose Separator (GPS). [3] Alternatively, the facility uses pre-irradiated targets that are provided by external institutions. [16] MEDICIS was one of the few facilities operating throughout the Long Shutdown 2, due to it being provided with 34 externally irradiated target materials. [3]

MEDICIS Promed training with Nobel prize winner, Kostya Novozelov MEDICIS Promed.jpg
MEDICIS Promed training with Nobel prize winner, Kostya Novozelov

Due to the high levels of radiation, the targets are transferred from the irradiation station to the radioisotope mass-separation beamline using an automated rail conveyer system (RCS). [1] [3] A KUKA robot is used to transport the target to the station, where the isotope of interest can be collected and radiochemically purified. [17] This is done by heating the target up to very high temperatures, often more than 2000 °C, which causes the specified isotopes to diffuse. The isotopes are then ionised and accelerated by an ion source to be sent through a mass separator. The mass separator extracts the isotope of interest so that it can be implanted onto thin gold foils with a one-sided metallic or salt coating. [18] [19]

In 2019, the MEDICIS Laser Ion Source Setup At CERN (MELISSA) became fully operational, containing the individual lasers, auxiliary and control systems, and optical beam transport. [20] The MELISSA laser laboratory has helped to successfully increase the separation efficiency and the yield of the isotopes. [16] [3] The laser excites only isotopes of the desired element, allowing an element-selective isotope separation for a given atomic mass from other isobars by the mass separator. [21]

A shielded trolley is used to retrieve the samples after the radioisotopes have been collected, in order to avoid risk of contamination. [19] Once the target is finished being used, it is sent to a hot cell in order to be safely dismantled and put in waste bins.

Glovebox at the nanolaboratory at MEDICIS MEDICIS Nanolab.jpg
Glovebox at the nanolaboratory at MEDICIS

Once collected, the samples can be sent to hospitals and research facilities with the purpose of developing patient imaging and treatment, and therapy protocols. [22]

Additionally next to the MEDICIS facility, there is a nanolab laboratory designed for the development and assembly of nanomaterials. [23] The nanomaterials are sealed in a glovebox, meaning there is no contact with the outside environment. [24] It builds up on the development of the first nanostructured targets used for isotope production, and further exploits developments initiated in MEDICIS-Promed under the guidance of Prof. "Kostya" Novozelov.

Projects and results

Targeted therapy

Several lanthanides produced at CERN-MEDICIS, samarium and terbium, are of interest for targeted therapy alike lutetium already used in the clinics. [25] Lutetium emits low energy β particles with a short range, used for irradiation of smaller volume tumor targets. [26] Terbium-149 emits short-range alpha particles, gamma-rays and positrons, in its decay scheme, which makes it suitable for targeted alpha therapy. The particular study of 149Tb produced by ISOLDE has been in folate receptor therapy, prominent in ovarian and lung cancer. [25] [27]

153Sm, produced in the BR2 reactor at SCK CEN, followed by the subsequent mass separation by MEDICIS to increase its molar activity, was found to be suitable for targeted radionuclide therapy (TRNT) in a proof-of-concept research project. [28] It emits low energy β particles and gamma peaks, and presents acceptable half-life for logistics and ambulatory care, making it a candidate of choice for theranostics approaches.

Theranostics

SPECT-CT images at (a) 4h post injection and (b) 24h post injection MEDICIS imaging.png
SPECT-CT images at (a) 4h post injection and (b) 24h post injection

Theranostics, a treatment that combines therapy and diagnosis, is a new trend in precision medicine where the radioisotopes produced at MEDICIS already triggered research projects. The strategy the facility uses is to find an element that has two radioisotopes, used for imaging and therapy separately. [29]

A promising element for use in theranostics is terbium as it has four different radioisotopes for use in therapy and PET or SPECT imaging. In 2021, Tb radioisotope production was successfully performed with the MELISSA laser ion source, with a 53% ionisation efficiency obtained by MEDICIS-Promed students. [30] Since 2021, three other non-conventional isotopes of interest for PET imaging or therapeutic applications have been produced. [31]

Exploration of mass separated 153Sm at MEDICIS using in vitro biological studies showed that the ability for tumors to absorb (uptake) and retain substances (retention) was improved compared to normal tissues. Animal SPECT-CT scans of mice were obtained post-injection and showed cleared activity after twenty-four hours. [32]

Involvement with PRISMAP

The PRoduction of high purity Isotopes by mass Separation for Medical APplication (PRISMAP) is the European medical radionuclide programme, with the goal to provide a sustainable source of high-purity radioisotopes for medicine. [33] [34] The programme brings together 23 beneficiaries from 13 countries, to create a single entry point for the medical isotope user community. [35] The MEDICIS facility provides mass separation of isotopes, which can then be transported to nearby research facilities hosting external researchers to limit long haul transport of the samples. [36]

Related Research Articles

Isotope separation is the process of concentrating specific isotopes of a chemical element by removing other isotopes. The use of the nuclides produced is varied. The largest variety is used in research. By tonnage, separating natural uranium into enriched uranium and depleted uranium is the largest application. In the following text, mainly uranium enrichment is considered. This process is crucial in the manufacture of uranium fuel for nuclear power plants and is also required for the creation of uranium-based nuclear weapons. Plutonium-based weapons use plutonium produced in a nuclear reactor, which must be operated in such a way as to produce plutonium already of suitable isotopic mix or grade.

A radionuclide (radioactive nuclide, radioisotope or radioactive isotope) is a nuclide that has excess numbers of either neutrons or protons, giving it excess nuclear energy, and making it unstable. This excess energy can be used in one of three ways: emitted from the nucleus as gamma radiation; transferred to one of its electrons to release it as a conversion electron; or used to create and emit a new particle (alpha particle or beta particle) from the nucleus. During those processes, the radionuclide is said to undergo radioactive decay. These emissions are considered ionizing radiation because they are energetic enough to liberate an electron from another atom. The radioactive decay can produce a stable nuclide or will sometimes produce a new unstable radionuclide which may undergo further decay. Radioactive decay is a random process at the level of single atoms: it is impossible to predict when one particular atom will decay. However, for a collection of atoms of a single nuclide the decay rate, and thus the half-life (t1/2) for that collection, can be calculated from their measured decay constants. The range of the half-lives of radioactive atoms has no known limits and spans a time range of over 55 orders of magnitude.

A synthetic radioisotope is a radionuclide that is not found in nature: no natural process or mechanism exists which produces it, or it is so unstable that it decays away in a very short period of time. Frédéric Joliot-Curie and Irène Joliot-Curie were the first to produce a synthetic radioisotope in the 20th century. Examples include technetium-99 and promethium-146. Many of these are found in, and harvested from, spent nuclear fuel assemblies. Some must be manufactured in particle accelerators.

<span class="mw-page-title-main">TRIUMF</span> Particle physics laboratory in Canada

TRIUMF is Canada's national particle accelerator centre. It is considered Canada's premier physics laboratory, and consistently regarded as one of the world's leading subatomic physics research centres. Owned and operated by a consortium of universities, it is on the south campus of one of its founding members, the University of British Columbia in Vancouver, British Columbia, Canada. It houses the world's largest normal conducting cyclotron, a source of 520 MeV protons, which was named an IEEE Milestone in 2010. Its accelerator-focused activities involve particle physics, nuclear physics, nuclear medicine, materials science, and detector and accelerator development.

<span class="mw-page-title-main">Radiopharmacology</span> Pharmacologic study of radiated medical compounds

Radiopharmacology is radiochemistry applied to medicine and thus the pharmacology of radiopharmaceuticals. Radiopharmaceuticals are used in the field of nuclear medicine as radioactive tracers in medical imaging and in therapy for many diseases. Many radiopharmaceuticals use technetium-99m (Tc-99m) which has many useful properties as a gamma-emitting tracer nuclide. In the book Technetium a total of 31 different radiopharmaceuticals based on Tc-99m are listed for imaging and functional studies of the brain, myocardium, thyroid, lungs, liver, gallbladder, kidneys, skeleton, blood and tumors.

<span class="mw-page-title-main">ISOLDE</span> Physics facility at CERN

The ISOLDE Radioactive Ion Beam Facility, is an on-line isotope separator facility located at the centre of the CERN accelerator complex on the Franco-Swiss border. Created in 1964, the ISOLDE facility started delivering radioactive ion beams (RIBs) to users in 1967. Originally located at the Synchro-Cyclotron (SC) accelerator, the facility has been upgraded several times most notably in 1992 when the whole facility was moved to be connected to CERN's ProtonSynchroton Booster (PSB). ISOLDE is currently the longest-running facility in operation at CERN, with continuous developments of the facility and its experiments keeping ISOLDE at the forefront of science with RIBs. ISOLDE benefits a wide range of physics communities with applications covering nuclear, atomic, molecular and solid-state physics, but also biophysics and astrophysics, as well as high-precision experiments looking for physics beyond the Standard Model. The facility is operated by the ISOLDE Collaboration, comprising CERN and sixteen (mostly) European countries. As of 2019, close to 1,000 experimentalists around the world are coming to ISOLDE to perform typically 50 different experiments per year.

Naturally occurring terbium (65Tb) is composed of one stable isotope, 159Tb. Thirty-seven radioisotopes have been characterized, with the most stable being 158Tb with a half-life of 180 years, 157Tb with a half-life of 71 years, and 160Tb with a half-life of 72.3 days. All of the remaining radioactive isotopes have half-lives that are less than 6.907 days, and the majority of these have half-lives that are less than 24 seconds. This element also has 27 meta states, with the most stable being 156m1Tb, 154m2Tb and 154m1Tb.

<span class="mw-page-title-main">Proton Synchrotron Booster</span> CERN particle accelerator

The Proton Synchrotron Booster (PSB) is the first and smallest circular proton accelerator in the accelerator chain at the CERN injection complex, which also provides beams to the Large Hadron Collider. It contains four superimposed rings with a radius of 25 meters, which receive protons with an energy of 160 MeV from the linear accelerator Linac4 and accelerate them up to 2.0 GeV, ready to be injected into the Proton Synchrotron (PS). Before the PSB was built in 1972, Linac 1 injected directly into the Proton Synchrotron, but the increased injection energy provided by the booster allowed for more protons to be injected into the PS and a higher luminosity at the end of the accelerator chain.

Indium-111 (111In) is a radioactive isotope of indium (In). It decays by electron capture to stable cadmium-111 with a half-life of 2.8 days. Indium-111 chloride (111InCl) solution is produced by proton irradiation of a cadmium target in a cyclotron, as recommended by International Atomic Energy Agency (IAEA). The former method is more commonly used as it results in a high level of radionuclide purity.

<span class="mw-page-title-main">Saul Hertz</span> American physician-scientist

Saul Hertz, M.D. was an American physician who devised the medical uses of radioactive iodine. Hertz pioneered the first targeted cancer therapies. Hertz is called the father of the field of theranostics, combining diagnostic imaging with therapy in a single or paired chemical substance(s).

The Sarayköy Nuclear Research and Training Center, known as SANAEM, is a nuclear research and training center of Turkey. The organization was established on July 1, 2005, as a subunit of Turkish Atomic Energy Administration at Kazan district in northwest of Ankara on an area of 42.3 ha.

The Synchro-Cyclotron, or Synchrocyclotron (SC), built in 1957, was CERN’s first accelerator. It was in circumference and provided for CERN's first experiments in particle and nuclear physics. It accelerated particles to energies up to 600 MeV. The foundation stone of CERN was laid at the site of the Synchrocyclotron by the first Director-General of CERN, Felix Bloch. After its remarkably long 33 years of service time, the SC was decommissioned in 1990. Nowadays it accepts visitors as an exhibition area in CERN.

<span class="mw-page-title-main">COLLAPS experiment</span>

The COLinear LAser SPectroscopy (COLLAPS) experiment is located in the ISOLDE facility at CERN. The purpose of the experiment is to investigate ground and isomeric state properties of exotic, short lived nuclei, including spins, electro-magnetic moments and charge radii. The experiment has been operating since the late 1970s, and is the oldest active experiment at ISOLDE.

<span class="mw-page-title-main">CRIS experiment</span>

The Collinear Resonance Ionization Spectroscopy (CRIS) experiment is located in the ISOLDE facility at CERN. The experiment aims to study ground-state properties of exotic nuclei and produce high purity isomeric beams used for decay studies. CRIS does this by using the high resolution technique of fast beam collinear laser spectroscopy, with the high efficiency technique of resonance ionization.

<span class="mw-page-title-main">ISOLDE Decay Station experiment</span>

The ISOLDE Decay Station (IDS) is a permanent experiment located in the ISOLDE facility at CERN. The purpose of the experiment is to measure decay properties of radioactive isotopes using spectroscopy techniques for a variety of applications, including nuclear engineering and astrophysics. The experimental setup has been operational since 2014.

<span class="mw-page-title-main">ISOLDE Solenoidal Spectrometer experiment</span>

The ISOLDE Solenoidal Spectrometer (ISS) experiment is a permanent experimental setup located in the ISOLDE facility at CERN. By using an ex-MRI magnet, heavy radioactive ion beams (RIBs) produced by the HIE-ISOLDE post-accelerator are directed at a light target and the kinematics of the reaction is measured. The purpose of the experiment is to measure properties of atomic nuclei replicating the conditions present in some astrophysical processes, such as the production of chemical elements in stars. The experiment will also produce results that provide a better understanding of nucleon-nucleon interactions in highly-unstable, very radioactive (exotic) nuclei.

<span class="mw-page-title-main">ISOLTRAP experiment</span>

The high-precision mass spectrometer ISOLTRAP experiment is a permanent experimental setup located at the ISOLDE facility at CERN. The purpose of the experiment is to make precision mass measurements using the time-of-flight (ToF) detection technique. Studying nuclides and probing nuclear structure gives insight into various areas of physics, including astrophysics.

<span class="mw-page-title-main">MIRACLS experiment</span>

The Multi Ion Reflection Apparatus for Colinear Laser Spectroscopy (MIRACLS) is a permanent experiment setup being constructed at the ISOLDE facility at CERN. The purpose of the experiment is to measure properties of exotic radioisotopes, from precise measurements of their hyperfine structure. MIRACLS will use laser spectroscopy for measurements, aiming to increase the sensitivity of the technique by trapping ion bunches in an ion trap.

<span class="mw-page-title-main">VITO experiment</span>

The Versatile Ion polarisation Technique Online (VITO) experiment is a permanent experimental setup located in the ISOLDE facility at CERN, in the form of a beamline. The purpose of the beamline is to perform a wide range of studies using spin-polarised short-lived atomic nuclei. VITO uses circularly-polarised laser light to obtain polarised radioactive beams of different isotopes delivered by ISOLDE. These have already been used for weak-interaction studies, biological investigations, and more recently nuclear structure research. The beamline is located at the site of the former Ultra High Vacuum (UHV) beamline hosting ASPIC.

References

  1. 1 2 "MEDICIS shows its strength". CERN Courier. 2020-12-18. Retrieved 2023-07-10.
  2. ↑ "CERN-MEDICIS produces first medical isotopes". Physics World. 2017-12-13. Retrieved 2023-07-10.
  3. 1 2 3 4 5 6 Duchemin, Charlotte; Ramos, Joao P.; Stora, Thierry; Ahmed, Essraa; Aubert, Elodie; Audouin, Nadia; Barbero, Ermanno; Barozier, Vincent; Bernardes, Ana-Paula; Bertreix, Philippe; Boscher, Aurore; Bruchertseifer, Frank; Catherall, Richard; Chevallay, Eric; Christodoulou, Pinelopi (2021). "CERN-MEDICIS: A Review Since Commissioning in 2017". Frontiers in Medicine. 8: 693682. doi: 10.3389/fmed.2021.693682 . PMC   8319400 . PMID   34336898.
  4. ↑ Pixels 2, Rockin (2018-01-02). "The new CERN facility can contribute towards cancer research". Foro Nuclear. Retrieved 2023-07-11.{{cite web}}: CS1 maint: numeric names: authors list (link)
  5. ↑ Bernardes, A P (15 Oct 2014). "Integrating Safety into MEDICIS project" (PDF). Retrieved 24 July 2023.
  6. 1 2 "Radioisotopes in Medicine | Nuclear Medicine - World Nuclear Association". www.world-nuclear.org. Retrieved 2023-07-17.
  7. ↑ Drozdovitch, Vladimir; Brill, Aaron B.; Callahan, Ronald J.; Clanton, Jeffrey A.; DePietro, Allegra; Goldsmith, Stanley J.; Greenspan, Bennett S.; Gross, Milton D.; Hays, Marguerite T.; Moore, Stephen C.; Ponto, James A.; Shreeve, Walton W.; Melo, Dunstana R.; Linet, Martha S.; Simon, Steven L. (May 2015). "Use of Radiopharmaceuticals in Diagnostic Nuclear Medicine in the United States: 1960–2010". Health Physics. 108 (5): 520–537. doi:10.1097/HP.0000000000000261. ISSN   0017-9078. PMC   4376015 . PMID   25811150.
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  15. ↑ Brown, Alexander (1 September 2015). Design of the CERN MEDICIS Collection and Sample Extraction System. University of Manchester (Thesis).
  16. 1 2 Gadelshin, V. M.; Barozier, V.; Cocolios, T. E.; Fedosseev, V. N.; Formento-Cavaier, R.; Haddad, F.; Marsh, B.; Marzari, S.; Rothe, S.; Stora, T.; Studer, D.; Weber, F.; Wendt, K. (2020-01-15). "MELISSA: Laser ion source setup at CERN-MEDICIS facility. Blueprint". Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms. 463: 460–463. Bibcode:2020NIMPB.463..460G. doi:10.1016/j.nimb.2019.04.024. ISSN   0168-583X. S2CID   182312164.
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  18. ↑ Duchemin, Charlotte; Barbero-Soto, Esther; Bernardes, Ana; Catherall, Richard; Chevallay, Eric; Cocolios, Thomas; Dorsival, Alexandre; Fedosseev, Valentin; Fernier, Pascal; Gilardoni, Simone; Grenard, Jean-Louis; Haddad, Ferid; Heinke, Reinhard; Khan, Muhammad Asif; Lambert, Laura (2020). "CERN-MEDICIS: A Unique Facility for the Production of Non-Conventional Radionuclides for the Medical Research". Proceedings of the 11th International Particle Accelerator Conference. IPAC2020. Seidel Mike (Ed.), Aßmann, Ralph W. (Ed.), Chautard Frédéric (Ed.), Schaa, Volker R.W. (Ed.): 5 pages, 0.595 MB. doi:10.18429/JACOW-IPAC2020-THVIR13. ISSN   2673-5490.
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  25. 1 2 Burkhardt, Claudia; Bühler, Léo; Viertl, David; Stora, Thierry (2021-08-02). "New Isotopes for the Treatment of Pancreatic Cancer in Collaboration With CERN: A Mini Review". Frontiers in Medicine. 8: 674656. doi: 10.3389/fmed.2021.674656 . ISSN   2296-858X. PMC   8365147 . PMID   34409048.
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  27. ↑ Müller, Cristina; Reber, Josefine; Haller, Stephanie; Dorrer, Holger; Köster, Ulli; Johnston, Karl; Zhernosekov, Konstantin; Türler, Andreas; Schibli, Roger (2014-03-13). "Folate Receptor Targeted Alpha-Therapy Using Terbium-149". Pharmaceuticals. 7 (3): 353–365. doi: 10.3390/ph7030353 . ISSN   1424-8247. PMC   3978496 . PMID   24633429.
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  30. ↑ Gadelshin, Vadim Maratovich; Formento Cavaier, Roberto; Haddad, Ferid; Heinke, Reinhard; Stora, Thierry; Studer, Dominik; Weber, Felix; Wendt, Klaus (2021). "Terbium Medical Radioisotope Production: Laser Resonance Ionization Scheme Development". Frontiers in Medicine. 8: 727557. doi: 10.3389/fmed.2021.727557 . PMC   8546115 . PMID   34712678.
  31. ↑ Bernerd, C.; Johnson, J. D.; Aubert, E.; Au, M.; Barozier, V.; Bernardes, A. -P.; Bertreix, P.; Bruchertseifer, F.; Catherall, R.; Chevallay, E.; Chrysalidis, K.; Christodoulou, P.; Cocolios, T. E.; Crepieux, B.; Deschamps, M. (2023-09-01). "Production of innovative radionuclides for medical applications at the CERN-MEDICIS facility". Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms. 542: 137–143. Bibcode:2023NIMPB.542..137B. doi:10.1016/j.nimb.2023.05.008. ISSN   0168-583X. S2CID   259717417.
  32. ↑ Vermeulen, Koen; Van de Voorde, Michiel; Segers, Charlotte; Coolkens, Amelie; Rodriguez Pérez, Sunay; Daems, Noami; Duchemin, Charlotte; Crabbé, Melissa; Opsomer, Tomas; Saldarriaga Vargas, Clarita; Heinke, Reinhard; Lambert, Laura; Bernerd, Cyril; Burgoyne, Andrew R.; Cocolios, Thomas Elias (Dec 2022). "Exploring the Potential of High-Molar-Activity Samarium-153 for Targeted Radionuclide Therapy with [153Sm]Sm-DOTA-TATE". Pharmaceutics. 14 (12): 2566. doi: 10.3390/pharmaceutics14122566 . ISSN   1999-4923. PMC   9785812 . PMID   36559060.
  33. ↑ MEDICIS. "PRISMAP The European medical isotope programme" (PDF). medicis.cern. Retrieved 12 July 2023.
  34. ↑ "Project description". PRISMAP. Retrieved 2023-07-12.
  35. ↑ "PRISMAP Call for Projects". EANM. 2021-12-17. Retrieved 2023-07-12.
  36. ↑ "PRISMAP – The European medical radionuclides programme sets out to transform the European landscape for novel and emerging medical radionuclides - ILL Neutrons for Society". www.ill.eu. Retrieved 2023-07-12.
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