The ISOLPHARM project: ISOL-based production of radionuclides for medical applications

Andrighetto, A.; Tosato, Marianna; Ballan, M.; Corradetti, S.; Borgna, Francesca; Marco, Valerio Di; Marzaro, Giovanni; Realdon, Nicola

doi:10.1007/s10967-019-06698-0

Cited by 22 publications

(11 citation statements)

References 17 publications

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Section: Introductionmentioning

confidence: 99%

“…Direct production via 110 Pd(d,n) 111 Pd is also possible with access to medium energy deuteron beams (10–20 MeV) . As an alternative route, the 111 Ag production via Isotope Separation Online (ISOL) technique is being investigated at the Legnaro National Laboratories of the Italian Institute of Nuclear Physics (ISOLPHARM project). , …”

Section: Introductionmentioning

confidence: 99%

“…14 As an alternative route, the 111 Ag production via Isotope Separation Online (ISOL) technique is being investigated at the Legnaro National Laboratories of the Italian Institute of Nuclear Physics (ISOLPHARM project). 25,26 Only limited preclinical applications of 111 Ag are reported in the literature so far, 15,16 but to the best of our knowledge no previous research has investigated 111 Ag for its application in TRT. A key step to attain this goal is to develop suitable ligands that can act as BFCs forming sufficiently stable Ag + complexes under in vivo conditions.…”

Section: ■ Introductionmentioning

confidence: 99%

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Highly Stable Silver(I) Complexes with Cyclen-Based Ligands Bearing Sulfide Arms: A Step Toward Silver-111 Labeled Radiopharmaceuticals

et al. 2020

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With a half-life of 7.45 days, silver-111 (β max 1.04 MeV, E γ 245.4 keV [ I γ 1.24%], E γ 342.1 keV [ I γ 6.7%]) is a promising candidate for targeted cancer therapy with β – emitters as well as for associated SPECT imaging. For its clinical use, the development of suitable ligands that form sufficiently stable Ag + -complexes in vivo is required. In this work, the following sulfur-containing derivatives of tetraazacyclododecane (cyclen) have been considered as potential chelators for silver-111: 1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO4S), (2S,5S,8S,11S)-2,5,8,11-tetramethyl-1,4,7,10-tetrakis(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO4S4Me), 1,4,7-tris(2-(methylsulfanyl)ethyl)-1,4,7,10-tetraazacyclododecane (DO3S), 1,4,7-tris(2-(methylsulfanyl)ethyl)-10-acetamido-1,4,7,10-tetraazacyclododecane (DO3SAm), and 1,7-bis(2-(methylsulfanyl)ethyl)-4,10,diacetic acid-1,4,7,10-tetraazacyclododecane (DO2A2S). Natural Ag + was used in pH/Ag-potentiometric and UV–vis spectrophotometric studies to determine the metal speciation existing in aqueous NaNO 3 0.15 M at 25 °C and the equilibrium constants of the complexes, whereas NMR and DFT calculations gave structural insights. Overall results indicated that sulfide pendant arms coordinate Ag + allowing the formation of very stable complexes, both at acidic and physiological pH. Furthermore, radiolabeling, stability in saline phosphate buffer, and metal-competition experiments using the two ligands forming the strongest complexes, DO4S and DO4S4Me, were carried out with [ 111 Ag]Ag + and promising results were obtained.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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Highly Stable Silver(I) Complexes with Cyclen-Based Ligands Bearing Sulfide Arms: A Step Toward Silver-111 Labeled Radiopharmaceuticals

et al. 2020

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“…For this reason, the first studies on silver ionization were performed by using the SPES Plasma Ion Source, achieving an ionization efficiency of up to 16%. Once switched to RLI, the process will be more selective because only the isotopes of the same element will be ionized; thus, eventual isobaric contaminants will be excluded from the following beam of the selected isotope, achieving extremely high purity in the final product [17].…”

Section: Isol Production: Silver Ionization Detection and Depositionmentioning

confidence: 99%

A New Production Method of High Specific Activity Radionuclides Towards Innovative Radiopharmaceuticals: The Isolpharm Project

Vettorato¹,

Morselli²,

Ballan³

et al. 2022

RAD Conference Proceedings

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Radionuclides of interest in nuclear medicine are generally produced in cyclotrons or nuclear reactors, with associated issues such as highly enriched target costs and undesired contaminants. The ISOLPHARM project (ISOL technique for radioPHARMaceuticals) explores the feasibility of producing extremely high specific activity βemitting radionuclides as radiopharmaceutical precursors. This technique is expected to produce radiopharmaceuticals very hardly obtained in standard production facilities. Radioactive isotopes will be obtained from nuclear reactions induced by accelerating 40 MeV protons in a cyclotron to collide on a UCx target. By means of: high working temperatures and high vacuum conditions, the migration of the radioactive elements towards an ion source, a potential difference up to 40 kV, and a mass separation device, an isobaric beam of desired radionuclides will be produced and implanted on a deposition target. The availability of innovative isotopes can potentially open a new generation of radiopharmaceuticals, based on nuclides never studied so far. Among these, a very promising isotope could be Ag-111, a βemitter with a half-life (7.45 d), an average βenergy of 360 keV, a tissue penetration of around 1 mm, and a low percentage of γ-emission. The proof of principle studies on Ag-111 production and radiolabeling are currently under investigation in the ISOLPHARM_EIRA project, where both its production and possible application as a radiopharmaceutical precursor will be evaluated in its computational/physics, radiochemistry, and radiobiology tasks. Currently, innovative macromolecules meeting the specific requirements for the chelation and targeted delivery of Ag-111 are being developed, which will be further tested in vitro on 2D and 3D models, as well as in vivo for their pharmacokinetics and therapeutic potential onto xenograft models.

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“…161 Tb can also be produced after bombardment of neutrons on highly enriched 160 Gd targets at spallation neutron source (SINQ) of Paul Scherrer Institute (PSI), Switzerland or at a highflux nuclear reactor at Laue-Langevin (ILL) situated in France (57). The SPES-ISOLPHARM facility in Italy is also planning to produce 152 Tb, 155 Tb, 156 Tb, 161 Tb radioisotopes by high flux protons bombardment on Gd targets (58).…”

Section: Production Of Terbium Radionuclides By Spallation Reactionmentioning

confidence: 99%

Theranostic Terbium Radioisotopes: Challenges in Production for Clinical Application

Naskar

Lahiri

2021

Front. Med.

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Currently, research on terbium has gained a momentum owing to its four short-lived radioisotopes, 149Tb, 152Tb, 155Tb, and 161Tb, all of which can be considered in one or another field of nuclear medicine. The members of this emerging quadruplet family have appealing nuclear characteristics and have the potential to do justice to the proposed theory of theranostics nuclear medicine, which amalgamates therapeutic and diagnostic radioisotopes together. The main challenge for in vivo use of these radioisotopes is to produce them in sufficient quantity. This review discusses that, at present, neither light charged particle nor the heavy ion (HI) activation are suitable for large-scale production of neutron deficient terbium nuclides. Three technological factors like (i) enrichment of stable isotopes to a considerable level, (ii) non-availability of higher energies in commercial cyclotrons, and (iii) non-availability of the isotope separation technique coupled with commercial accelerators limit the large scale production of terbium radionuclides by light charged particle activation. If in future, the technology can overcome these hurdles, then the light charged particle activation of enriched targets would produce a high amount of useful terbium radionuclides. On the other hand, to date, the spallation reaction coupled with an online isotope separator has been found suitable for such a requirement, which has been adopted by the CERN MEDICIS programme. The therapeutic 161Tb radionuclide can be produced in a reactor by neutron bombardment on enriched 160Gd target to produce 161Gd which subsequently decays to 161Tb. The radiochemical separation is mandatory even if the ISOL technique is used to obtain high radioisotopic purity of the desired radioisotope.

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The ISOLPHARM project: ISOL-based production of radionuclides for medical applications

Cited by 22 publications

References 17 publications

Highly Stable Silver(I) Complexes with Cyclen-Based Ligands Bearing Sulfide Arms: A Step Toward Silver-111 Labeled Radiopharmaceuticals

Highly Stable Silver(I) Complexes with Cyclen-Based Ligands Bearing Sulfide Arms: A Step Toward Silver-111 Labeled Radiopharmaceuticals

A New Production Method of High Specific Activity Radionuclides Towards Innovative Radiopharmaceuticals: The Isolpharm Project

Theranostic Terbium Radioisotopes: Challenges in Production for Clinical Application

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