Technological advances in molecular biology and biotechnology are increasingly used for the development of new tumor targeting tracers. In oncology, major progress has recently been achieved with peptidic and small molecule compounds. This relies on the identification and validation of new target structures in close conjunction with the application of new techniques for the development of new...
With translation of new radioligands into clinical theragnostic practice, the therapeutic branch of nuclear medicine has gained fundamental momentum. The agonist-to-antagonist change in paradigm for different peptide receptor targeting systems is another current issue of major relevance. PSMA-targeted approaches are being discussed as role model treatment approach. Understanding the mechanism...
Glioblastoma multiforme (GBM) [World Health Organization (WHO) grade IV astrocytoma] is the most malignant form of brain tumors, carrying a poor prognosis and high rate of recurrence. During the course of the disease, microglia and brain macrophages are both recruited by the tumor microenvironment via the release of several chemoattractants and contribute considerably in several aspects of...
Molecular imaging systems (PET, SPECT) have been improved over the last 20 years using small changes in either reconstruction methods, collimator or detector. The availability of highy sampled Silicon multipliers and advanced positioning algorithms (Maximum Likelihood, Deep learning,..) lead to scintillation detectors with sub mm transverse resolution (at competitive cost with older PMT based...
In the case of emerging radiopharmaceuticals, the accuracy and precision of the decay data of the radionuclide is crucially important. These data, particularly particle emission probabilities and the half-life, are necessary for the correct quantification of PET images and for dosimetry considerations of practitioners and patient alike.
Often precise nuclear data is determined through a...
Ovarian cancer is the 8th most common cancer in women and the 5th most common reason for cancer death. There is no recognized screening method and ovarian cancer is most often diagnosed at an advanced stage. I will give a short background on epidemiology of epithelial ovarian cancer as well as on its diagnosis and genetic background. Then, we will discuss current standard treatment which...
Ovarian cancer is the most lethal gynecologic malignancy and it has high rate of recurrence justifying the development of new therapeutic tools. Our project aims at developing new radiopharmaceuticals and innovative route of administration to target the small volume residual disease after complete cytoreductive surgery of peritoneal carcinomatosis on preclinical models. We use internalising...
Aim. To assess the feasibility of mouse-specific, microPET- based dosimetry of an antibody labelled with 152Tb. Image-based absorbed dose estimates were compared with dosimetry results obtained from the extrapolation to 152Tb of a classical biodistribution experiment using the same antibody fragment labelled with 111In.
Methods. The scFv78-Fc fusion protein targeting TEM-1 was...
Introduction: Targeted radionuclide therapy using 161Tb is a promising approach for β- and Auger electron therapy.1 Moreover, the availability of the diagnostic radionuclides 152/155Tb is of interest in a theranostic setting.2-4 Heat-sensitive biomolecules (e.g. antibody fragments, etc.) are increasingly being used as carriers in radiometal-based radiopharmaceuticals. These molecules,...
Objectives: Targeted α-radionuclide therapy is a promising cancer therapy that allows targeted irradiation of primary tumour and its metastases. 213Bi-DOTATATE targeting the somatostatin receptor has been reported to delay growth in small and large volume endocrine tumours in mice (1,2). However, DOTA chelator has poor labelling kinetics and radiochemical purity with Bismuth-213. It...
The TEM1/endosialin is a receptor over-expressed in several human solid tumours and silenced in normal adult tissues, representing a suitable and potentially safe target for radioimmunotherapy of sarcoma.1,2 Taking advantage of the very fast in vivo kinetic of the click reaction between tetrazines (Tz) and trans-cyclooctene (TCO), we intent to explore a pre-targeting approach for the...
Ovarian cancer represents the most common cause of gynecological cancer death with a 5-year relative survival rate of 29% for patients diagnosed at a metastasized stage (1). The development of new treatment options is urgently needed to treat patients with refractory disease and platinum-resistance (1).
The folate receptor (FR) is overexpressed on the cell surface of a variety of tumors...
Approximately, 10-30% of ovarian cancers have an amplification of the human epidermal growth factor receptor type 2 (HER2) gene or overexpression of its protein product, while it is present at low levels in normal tissues. HER2 is a 185 kDa transmembrane protein that belongs to the HER family of tyrosine kinase receptors. Although controversial, recent studies have confirmed that HER2...
There has been increasing interest in four radioisotopes of terbium with the potential for use in nuclear medicine: 161Tb emits therapeutic beta and Auger particles; 155Tb emits gamma-rays suited to Single-Photon Emission Computed Tomography (SPECT); 152Tb emits positrons suitable for Positron Emission Tomography (PET); and 149Tb emits alpha particles suitable for therapy. Their identical...
Molecular imaging affords valuable information about biological processes at the molecular and cellular levels within complex living organisms and can help in earlier diagnostics of various diseases. Optical imaging modalities such as fluorescence imaging play a key role for preclinical research. Furthermore, new fluorescence imaging tools have a potential for clinical translation.
In this...
Auger electron emitters are promising candidates for targeted radionuclide therapy. They decay by internal conversion or electron capture, resulting in Auger cascades with the emission of several low energy (eV-keV) electrons. The multiplicity of electrons combined with their short range (nm-μm) results in a high local energy deposition density near the decay site. Decays happening close to...
Ovarian cancer is the fifth most lethal cancer among women. Early detection is highly warranted in order to optimize therapy, and improve the overall prognosis. However, technologies for early detection of ovarian cancer are currently lacking.
Here, we describe the development of a new dual imaging probe for ovarian cancer. This imaging probe is based on folate as targeting moiety. Our probe...
Radiotherapy using accelerated heavy ions has the potential to overhaul cancer treatment and replace invasive techniques (surgery, catheter ablation) for selected noncancer diseases. However, particle therapy is hampered by the range uncertainty and requires more precision to fully leverage its physical advantages and expand the applications to noncancer diseases such as heart arrhythmia. The...
The relativistic high-energy heavy-ion beam gives the good localized dose distribution and the large relative biological effectiveness, thus twelve heavy-ion radiotherapy (HIRT) facilities are under operation and six are under commissioning or construction worldwide. HIRT awakens worldwide interest. It is expected that clinical results will be improved through the more concentrated dose...
Formally the neutron is the lightest radionuclide on the bottom left corner of the chart of nuclides. However, in the present context their radioactive decay is not of concern but their interaction with biological tissue. In contrast to the charged particle beams used for hadron therapy, neutrons as neutral particles are not directly ionizing. However, neutron beams can be used for boron...
The particle therapy is a major contributor to the medical application of accelerator technology and may yet be improved by the use of radioisotopes as beam species, which would allow a better traceability of the applied dose.
The Medicis-Promed network leads an initiative to study the possible technical solutions for the implementation of Carbon-11 radioisotopes in an accelerator-based...
Within the Marie Skłodowska-Curie innovative training network MEDICIS-Promed, a $^{11}$C based carbon therapy protocol is being developed. Replacing the stable $^{12}$C beam with its radioactive isotope $^{11}$C, therapy can be combined with on-line PET-imaging. The PET-images that are recorded simultaneous with the treatment, represent a 3D dose distribution map of the irradiation field, and...
In this contribution, the possibilities of using a charge breeding scheme based on an Electron Beam Ion Source for beam preparation of a radioactive 11C beam for hadron therapy are discussed. Test measurements under extreme operating conditions were conducted at the REX-ISOLDE facility to explore the limitations of the charge breeder for high-intensity, low-repetition-rate, molecular CO+...
Radionuclides are used in different fields of medicine like oncology, neurology and cardiology, either for diagnostic or therapy. In most cases, radionuclides must be coupled to a carrier molecule to target the cells of interest. Many radionuclides may be of medical interest due to their emitted radiations (beta / alpha emitters, Auger emitters) and/or their half-lives that can be adapted to...
Much like at ISOLDE, the unused primary beam at the Facility for Rare Isotope Beams (FRIB) will retain a majority of its isotope-producing capability even after passing through the main target. In the spirit of MEDICIS, we are planning to make use of that unused capacity to access valuable radioisotopes for applications such as theranostics. This secondary isotope production will occur mainly...
Terbium is an element having four radioactive isotope of interest for nuclear medicine: Tb-149 and Tb-161 for therapy and Tb-152 and Tb-155 for imagery. The production of Tb-161 isotope can be done efficiently with high specific activity in nuclear reactor using Gd-161 target, the isotopes of Tb-149, Tb-152 and Tb-155 can be produced in a commercial cyclotron using a proton beam with energies...
ISOLPHARM [1] (ISOL technique for radioPHARMaceuticals) is a project devoted to the discovery and development of high specific activity radiopharmaceuticals exploiting radionuclides producible with the future SPES (Selective Production of Exotic Species) ISOL (Isotope Separation On-Line) facility at INFN-LNL.
The strength point of such production method is the capability to produce a wide set...
Radioisotopes of terbium (149, 152, 155, 161Tb) have been identified as a potential theranostic quartet for use in nuclear medicine. Any such radiopharmaceutical based on the radioisotopes would be required to have a low (< 0.1 %) level of radionuclidic impurities, therefore it is crucial that chemical separation techniques are developed to ensure these thresholds are met while maintaining a...
Er-169 (half-life 9.39 d) is an almost pure β- emitter characterized by low energy electrons emission and few low energy and very low intensity gamma rays. It is currently produced in nuclear reactors through the neutron activation of Er-168, which is one of the 6 natural erbium isotopes. Er-168 is commercially available at around 98% enrichment level; nevertheless, the cross section of the...
Abstract: Aerodynamic isotope separation in a free gas jet is enhanced by 2 orders of magnitude by laser-induced isotopically selective condensation. The method is quite generally applicable and is demonstrated for separating S, Br and Si isotopes. The separation of Mo isotopes is discussed in detail for the production of 100Mo for the 100Mo(p,2n)99Mo reaction and the production of 99mTc for...
The chemical vapour deposition (CVD) of graphene is the most promising route for the production of large-area graphene films. In this work, the growth of graphene on transition metals via CVD was investigated. The mechanisms of graphene formation on metals with different carbon solubility and therefore different affinity to carbon were observed and discussed.
In this work, three transition...
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Background: Radioactive ion beams at ISOLDE are produced by the interaction between an intense proton beam with a thick target material [1]. Micrometric UCx-based targets are the current reference at ISOLDE, but a significant increase on the yields of exotic isotopes is expected to be obtained from nanostructured and porous UCx targets.
Key Method: Electrospinning is a top-down...
Our developments on production of 165Er and 52Mn [1] for bimodal sensor MRI/PET or SPECT turn to be necessary an automatisation of separation process especially in case of 52Mn in terms of radiation protection. For that, a homemade system has been developed for purification of radiometal target especially for separation step with homemade software, ACCRA to remote control all operations. The...
ISOLPHARM-Ag is a branch of the SPES project (Selective Production of Exotic Species) aimed at the production of carrier free 111Ag for nuclear medicine application at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro). [1, 2]
Among all the radionuclides that will be produced by the future ISOL facility (Isotope Separation On Line), 111Ag is regarded as a very...
Folate-based radiopharmaceuticals were applied for targeting the folate receptor (FR) positive malignant tissue while cyclic Arg-Gly-Asp (c(RGD)) peptides were used to target αvβ3 integrin which is overexpressed during tumor angiogenesis. Combination of these two different targeting motifs in one molecule could be utilizable for dual-targeting. Here, we present the introduction of folate and...
Our goal is to contribute for the development of new strategies for prostate cancer theranostics, based on bombesin (BBN) analogues with very high affinity and specificity for the GRP receptor (GRPr) and on a multistep pretargeting strategy. To achieve this goal, we have opted by in vivo inverse-electron demand Diels-Alder (IEDDA) reactions between BBN antagonists carrying a trans-cyclooctene...
Gold nanoparticles (AuNPs) can play a pivotal role in the design of new theranostic tools for cancer treatment. This is due to their appealing properties for medical application such as, biocompatibility, easy functionalization with molecular vectors and good biological half-life. Additionally, AuNPs can also be explored as multifunctional platforms for targeted-delivery of radionuclides and...
Over the last few years, several studies have proven the effect of targeted alpha therapy using Ac-225 and Bi-213 [1, 2, 3]. One of the crucial bottlenecks in upscaling these studies and moving to clinical trials is the availability of these isotopes. The current production methods cannot provide sufficient quantities of Ac-225 or its daughter Bi-213. Furthermore, some of these production...
Four terbium isotopes (149Tb, 152Tb, 155Tb, and 161Tb) have been shown to possess physical and chemical properties suitable for all therapeutic and diagnostic applications in nuclear medicine[1]. If a diagnostic (e.g. 155Tb) and therapeutic (e.g. 161Tb) terbium isotope can be combined, then it would give theranostic pair with identical chemical properties. This is a particularly promising...
Radioisotopes are one of the essential cornerstones of modern medicine. They may be used for both diagnostic and therapeutic purposes. Here we present full describtion of a 12 MeV compact high field superconducting cyclotron with a magnetic field 2 times higher than conventional H- cyclotrons that has been developed recently. This cyclotron will be a modern, state of the art design, which,...
In a context of development of radiometals (165Er, 52Mn or 89Zr) for imaging applications at Orleans’ cyclotron, more regular and higher activities are necessary. For that, a new targetry was developed for solid target using a known cooling system [1] where target was in a shuttle. In this targetry, two measurements of temperature have been integrated: one by thermocouple on the backside of...
The medical use of radioactive isotopes for diagnosis and treatment is a publicly accepted and well supported success history. The rapid growth of molecular imaging, PET scanning and radionuclide therapy of cancer has increased the demand for isotope production across the globe. Unfortunately, we are also witnessing the decreased availability of large nuclear facilities due to aging facilities...
In this contribution, an overview will be given of the different cyclotrons and electron accelerators produced by Ion Beam Application (IBA, Louvain-la-Neuve, Belgium) for radio-isotope production.
The 3 main cyclotrons for radio-isotope production are distinguished by their maximum beam energy : the Cyclone KIUBE delivers protons up to 18 MeV, the Cyclone 30(XP) delivers protons from 15 up to...
The MEDICIS facility mission is to become a European leading facility and CERN's main producer of non-conventional medical isotopes for research in cancer treatment and diagnosis. Current isotopes produced at MEDICIS include: 149Tb, 152Tb, 155Tb, 169Er and 165Tm and developments are being made to extend this list to 47Sc, 44Sc, 67Cu and 225Ac. The isotopes are either produced with CERN’s 1.4...
At INFN-LNL (Istituto Nazionale di Fisica Nucleare – Laboratori Nazionali di Legnaro) a new facility for the production of radioactive ion beams is implemented, SPES (Selective Production of Exotic Species). This new facility, besides being operated for nuclear physics studies, may play a pivotal role in the production of medically relevant radionuclides by means of the ISOL (Isotope...
Molecular beams injected into the Radio-Frequency Quadrupole cooler and buncher (RFQcb), ISCOOL [1], at ISOLDE [2] have been studied under varying conditions. The extracted fragments were detected using the new Time-of-Flight (ToF) detector [3] placed approximately 10 meters downstream the extraction point of the RFQcb. When a beam of molecules is injected into the RFQcb and interacts with...
One limitation of the production of some radioisotope for medical use is the possibility to obtain them with a sufficient purity, not only in terms of chemical contaminant, but also in terms of isotopes. Different production techniques are available but at least for some particular isotopes, enriched primary matter is mandatory in order to achieve sufficient isotopic purity and not produce...
The state of the art in linac architecture at the low energy front has been developed quite a lot during the last decades. Frequency ranges and choices among available key components like amplifiers, controls and magnets have been extended. Room temperature as well as superconducting developments with high reliability are available now. The Pro's and Con's of alternative layouts will be...
The CERN-MEDICIS facility delivered its first radioactive batch for research in May 2018. Based on the ISOL method for radioactive ion beam production, MEDICIS relies on the CERN PS-Booster for target irradiation, but, unlike ISOLDE, it is not coupled ‘on-line’ to an isotope extraction system. Instead, targets are typically irradiated (while cold) at the ISOLDE proton beam dump location and...
The targeted treatment of cancerous tumors by alpha-emitting radionuclides has shown remarkable efficacy in recent clinical trials. It is likely that this treatment option will ultimately be applicable to a wide range of cancers and other diseases, subject to the development of specific carrier molecules. Currently Ac-225 is mainly produced from natural ingrowth in existing stocks of Th-229....
The Medicis isotope production process relies on a sequence of remote handling operations involving several different devices which have been integrated to work together. The handling sequence starts with the introduction of a new target in the Medicis facility for irradiation in Isolde and ends with the transfer of the collected isotopes into a fume cupboard in the Medicis laboratory area. ...
With over five decades of experience in the production of accelerator-based isotopes for science, TRIUMF also ensures that Canada remains on the leading edge of research and development of isotopes applied to nuclear medicine. TRIUMF’s medical isotope program is primed to develop alternative tools and methods to meet the growing demand for life-saving isotopes, and advance the design and...
The CERN-MEDICIS facility is aimed for the production of innovative medical radioisotopes. The dedicated electromagnetic mass separator allows to selectively extract a desired isotope from all others of the same element, what is inaccessible for chemical separation methods. It is foreseen to handle working materials, which are either irradiated at the CERN-ISOLDE target station or provided...
Type B packages are required for the transport of radionuclides with activity higher than the limits described by the current European Regulation1, named A1 and A2. The homologation for a Type B container can be obtained only after having proved, via strict tests described by the International Atomic Energy Agency (IAEA), the radioprotection and the mechanical resistance in normal and...
Radionuclides play a major role in research applications, in environmental studies and in industrial applications as sources as well as in nuclear medicine imaging and therapy. The United States Department of Energy (DOE) isotope program has a long history of utilizing its unique national laboratory facilities and expertise to develop and supply radionuclides that are in high demand and...
CERN-MEDICIS is a CERN facility dedicated to the production of isotopes for medical research in a very pure form. Such radioisotopes are produced in ISOLDE target production area by taking advantage of the 1.4Gev proton beam with low energy degradation which is still available after ISOLDE target interaction before reaching the dump. MEDICIS targets are designed to be larger than ISOLDE...
Trend of producing radionuclides for medical applications for both diagnostic and therapeutic purposes is on the rise. Amongst all medical radioisotopes, Mo-99/Tc-99m is the power hub of all nuclear medicines as it is being used in 80% of the nuclear procedures worldwide. I have been involved in production of Mo-99/Tc-99m Generators for the last twelve years in Pakistan. My institute is...
Our project is devoted to a new medical imaging modality based on a revolutionary technology combining the sensitivity of γ detection and the spatial resolution and flexibility of MRI. This modality, the so-called γ-MRI, goes beyond the present technological paradigms in molecular imaging. It is not just a hybrid approach joining two separate modalities into one complex machine (like for...
The Isotope Separator On-Line DEvice ISOLDE is a facility dedicated to the production of radioactive ion beams at CERN. With over 50 years of experience, ISOLDE is able to deliver more than 1000 different isotopes of 74 chemical elements used for experiments in various fields such as nuclear and atomic physics, material science and nuclear medicine.
Radionuclides are produced by irradiating...
