Medical isotopes from ISAC actinide targets

Kunz, P.; Andreoiu, C.; Crawford, Jason R.; Even, J.; Garcia, F. H.; Lambert, Laura; Lassen, J.; Radchenko, Valery; Ramogida, Caterina F.; Robertson, Andrew K. H.; Ruth, Thomas J.; Schaffer, Paul

doi:10.15669/pnst.5.4

Cited by 5 publications

(4 citation statements)

References 10 publications

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“…In our experience, this has made it challenging to plan more involved in vivo studies. As new sources of 225 Ac begin to emerge (11th International Symposium on Targeted Alpha Therapy (TAT11), 2019; Robertson et al 2017), medical radionuclide production at TRIUMF’s ISAC facility will transition towards less accessible radionuclides in order to harness the main advantage of ISOL facilities for medical isotope production – the flexibility to provide quick access to a diverse range of high-purity medical radionuclides without needing to establish radionuclide-specific production infrastructure or processes (Robertson et al 2018; dos Santos Augusto et al 2014; Kunz et al 2018). The limitations of ISAC-produced 225 Ac for preclinical research are highlighted by challenges associated with the 225 Ac-DOTA-CycMSH study: the relatively low levels of 225 Ac isolated by the ISOL method required the entire isolated 225 Ac fraction for one radiolabeling reaction to isolate enough purified radiotracer for one set of preclinical in vivo studies (see Additional file 1: Section S2).…”

Section: Discussionmentioning

confidence: 99%

“…Ion beams of 225 Ra and 225 Ac were created using the isotope separation on-line (ISOL) technique in operation at TRIUMF’s ISAC facility (Dilling et al 2014). Detailed descriptions of the collection of radioactivity from these beams is described elsewhere (Robertson et al 2018; Crawford et al 2017a; Crawford et al 2017b; Crawford et al 2018; Kunz et al 2018). Briefly, a uranium carbide target is bombarded with 9.8 μA of 480 MeV protons, which cause spallation, fission and fragmentation of the 238 U target atoms.…”

Section: Methodsmentioning

confidence: 99%

“…Efficient laser ionization schemes for Ac and Ra can now be applied at ISAC simultaneously for co-implantation of Ac and Ra. After implantation, the aluminum target containing the implanted radioactivity was removed from the beamline and the 225 Ra and 225 Ac retrieved from the aluminum material by etching the surface of the aluminum with 0.1 M HCl (~ 0.5 mL) as described previously (Kunz et al 2018).…”

Section: Methodsmentioning

confidence: 99%

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Evaluation of polydentate picolinic acid chelating ligands and an α-melanocyte-stimulating hormone derivative for targeted alpha therapy using ISOL-produced 225Ac

Ramogida

Robertson

Jermilova³

et al. 2019

EJNMMI radiopharm. chem.

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Background Actinium-225 ( 225 Ac, t 1/2 = 9.9 d) is a promising candidate radionuclide for use in targeted alpha therapy (TAT), though the currently limited global supply has hindered the development of a suitable Ac-chelating ligand and 225 Ac-radiopharmaceuticals towards the clinic. We at TRIUMF have leveraged our Isotope Separation On-Line (ISOL) facility to produce 225 Ac and use the resulting radioactivity to screen a number of potential 225 Ac-radiopharmaceutical compounds. Results MBq quantities of 225 Ac and parent radium-225 ( 225 Ra, t 1/2 = 14.8 d) were produced and separated using solid phase extraction DGA resin, resulting in a radiochemically pure 225 Ac product in > 98% yield and in an amenable form for radiolabeling of ligands and bioconjugates. Of the many polydentate picolinic acid (“pa”) containing ligands evaluated (H 4 octapa [N 4 O 4 ], H 4 CHX octapa [N 4 O 4 ], p- NO 2 -Bn-H 4 neunpa [N 5 O 4 ], and H 6 phospa [N 4 O 4 ]), all out-performed the current gold standard, DOTA for 225 Ac radiolabeling ability at ambient temperature. Moreover, a melanocortin 1 receptor-targeting peptide conjugate, DOTA-modified cyclized α-melanocyte-stimulating hormone (DOTA-CycMSH), was radiolabeled with 225 Ac and proof-of-principle biodistribution studies using B16F10 tumour-bearing mice were conducted. At 2 h post-injection, tumour-to-blood ratios of 20.4 ± 3.4 and 4.8 ± 2.4 were obtained for the non-blocking (molar activity [M.A.] > 200 kBq/nmol) and blocking (M.A. = 1.6 kBq/nmol) experiment, respectively. Conclusion TRIUMF’s ISOL facility is able to provide 225 Ac suitable for preclinical screening of radiopharmaceutical compounds; [ 225 Ac(octapa)] − , [ 225 Ac( CHX octapa)] − , and [ 225 Ac(DOTA-CycMSH)] may be good candidates for further targeted alpha therapy studies. Electronic supplementary material The online version of this article (10.1186/s41181-019-0072-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Evaluation of polydentate picolinic acid chelating ligands and an α-melanocyte-stimulating hormone derivative for targeted alpha therapy using ISOL-produced 225Ac

Ramogida

Robertson

Jermilova³

et al. 2019

EJNMMI radiopharm. chem.

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“…Previously, RIMS has been performed on-line for the separation of Ac from irradiated UC for pre-clinical studies 34 . When produced and separated on-line, the instantaneous yield rate in number of ions per second of Ac was measured 35 , however no collection efficiency could be calculated. Here, for the first time, the laser ionization efficiency and collection efficiency are measured for off-line RIMS of Ac at CERN MEDICIS.…”

Section: Introductionmentioning

confidence: 99%

Resonant laser ionization and mass separation of 225Ac

Johnson

Heines

Bruchertseifer

et al. 2023

Sci Rep

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Abstract$$^{225}$$ 225 Ac is a radio-isotope that can be linked to biological vector molecules to treat certain distributed cancers using targeted alpha therapy. However, developing $$^{225}$$ 225 Ac-labelled radiopharmaceuticals remains a challenge due to the supply shortage of pure $$^{225}$$ 225 Ac itself. Several techniques to obtain pure $$^{225}$$ 225 Ac are being investigated, amongst which is the high-energy proton spallation of thorium or uranium combined with resonant laser ionization and mass separation. As a proof-of-principle, we perform off-line resonant ionization mass spectrometry on two samples of $$^{225}$$ 225 Ac, each with a known activity, in different chemical environments. We report overall operational collection efficiencies of 10.1(2)% and 9.9(8)% for the cases in which the $$^{225}$$ 225 Ac was deposited on a rhenium surface and a ThO$$_{2}$$ 2 mimic target matrix respectively. The bottleneck of the technique was the laser ionization efficiency, which was deduced to be 15.1(6)%.

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