Production routes of the alpha emitting <sup>149</sup>Tb for medical application

Beyer, G.J.; Čomor, Jožef J.; Daković, Marko; Soloviev, D.; Tamburella, C.; Hagebø, E.; Allan, Barbara J.; Dmitriev, S. N.; Zaitseva, N.G.

doi:10.1524/ract.2002.90.5_2002.247

Cited by 63 publications

(48 citation statements)

References 14 publications

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“…An alternative to the production of 149 Tb and 152 Tb using protons would be heavy ion-induced reactions. These strategies were described and evaluated in detail recently (2,16). For the present study, 149 Tb, 152 Tb, and 155 Tb were produced by high-energy proton-induced spallation of tantalum, followed by online mass separation at ISOLDE facility CERN.…”

Section: Discussionmentioning

confidence: 99%

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β⁻-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

et al. 2012

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Terbium offers 4 clinically interesting radioisotopes with complementary physical decay characteristics: 149 Tb, 152 Tb, 155 Tb, and 161 Tb. The identical chemical characteristics of these radioisotopes allow the preparation of radiopharmaceuticals with identical pharmacokinetics useful for PET ( 152 Tb) and SPECT diagnosis ( 155 Tb) and for a-( 149 Tb) and b 2 -particle ( 161 Tb) therapy. The goal of this proof-of-concept study was to produce all 4 terbium radioisotopes and assess their diagnostic and therapeutic features in vivo when labeled with a folate-based targeting agent. Methods: 161 Tb was produced by irradiation of 160 Gd targets with neutrons at Paul Scherrer Institute or Institut LaueLangevin. After neutron capture, the short-lived 161 Gd decays to 161 Tb. 149 Tb, 152 Tb, and 155 Tb were produced by proton-induced spallation of tantalum targets, followed by an online isotope separation process at ISOLDE/CERN. The isotopes were purified by means of cation exchange chromatography. For the in vivo studies, we used the DOTA-folate conjugate cm09, which binds to folate receptor (FR)-positive KB tumor cells. Therapy experiments with 149 Tb-cm09 and 161 Tb-cm09 were performed in KB tumor-bearing nude mice. Diagnostic PET/ CT ( 152 Tb-cm09) and SPECT/CT ( 155 Tb-cm09 and 161 Tbcm09) studies were performed in the same tumor mouse model. Results: Carrier-free terbium radioisotopes were obtained after purification, with activities ranging from approximately 6 MBq (for 149 Tb) to approximately 15 GBq (for 161 Tb). The radiolabeling of cm09 was achieved in a greater than 96% radiochemical yield for all terbium radioisotopes. Biodistribution studies showed high and specific uptake in FR-positive tumor xenografts (23.8% 6 2.5% at 4 h after injection, 22.0% 6 4.4% at 24 h after injection, and 18.4% 6 1.8% at 48 h after injection). Excellent tumor-to-background ratios at 24 h after injection (tumor to blood, ;15; tumor to liver, ;5.9; and tumor to kidney, ;0.8) allowed the visualization of tumors in mice using PET ( 152 Tb-cm09) and SPECT ( 155 Tb-cm09 and 161 Tb-cm09). Compared with no therapy, a-( 149 Tb-cm09) and b 2 -particle therapy ( 161 Tb-cm09) resulted in a marked delay in tumor growth or even complete remission (33% for 149 Tb-cm09 and 80% for 161 Tb-cm09) and a significantly increased survival. Conclusion: Because of its physical half-lives (T 1/2 ), decay properties, and energies, the lanthanide terbium is one of the few elements that features 4 clinically interesting radioisotopes (Table 1). 149 Tb has a half-life of 4.12 h and emits shortrange a-particles at an energy (E a ) of 3.967 MeV with an intensity of 17%. It is the only a-emitter among radiolanthanides with a suitable half-life for application in radionuclide therapy. 152 Tb (T 1/2 , 17.5 h) emits positrons of an average energy of 1.080 MeV with an intensity of 17%. The radionuclide would be useful for patient-specific dosimetry using PET before the application of therapeutic radiolanthanides. 155 Tb (T 1/2 , 5.32 d) decays by electron cap...

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Section: Discussionmentioning

confidence: 99%

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β⁻-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

et al. 2012

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“…Beyer et al [9] separated nca 149 Tb from the other isobars and its decay products using cation exchange chromatography similar to that reported by Allen et al [8], dissolving the layer of KNO 3 containing the 149 Tb activity in 0.1 M HCl. The radionuclides were adsorbed on the AMINEX A5 resin and were transferred to the top of a small chromatographic column packed with the same resin in NH 4 + form.…”

Section: Introductionmentioning

confidence: 74%

“…The products of A = 152 were collected on high purity Al catcher. Beyer et al [9] produced nca 149 Tb as the decay product of 149 Dy by irradiating natural Nd 2 O 3 target by 108 MeV 12 C ions of 1 particle µA current for 75 min at the heavy ion cyclotron in the JINR, Dubna and achieved 2.7 MBq at the end of bombardment (EOB). They also produced 149 Tb via proton (E p = 1.4 GeV, beam current = 1-2 µA) induced spallation reaction on the Ta foil target with yield of 500 MBq using the ISOLDE facility at CERN.…”

Section: Introductionmentioning

confidence: 99%

Investigation on the production and isolation of ^149,150,151Tb from ¹²C irradiated natural praseodymium target

Maiti¹,

Lahiri

Tomar

2011

Radiochimica Acta

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Short lived α-emitting radionuclides have enormous potential to be used in the targeted therapy. 149Tb (4.118 h) is among the few α-emitting radionuclides which are projected for human clinical use. Therefore, direct production of 149Tb was aimed from the 12C induced reaction on natural praseodymium target of 15 mg∕cm2 thickness at 71.5 MeV incident beam energy. No-carrier-added (nca) 149,150,151Tb radionuclides were produced in the target matrix along with 149Gd, which is also the decay product of 149Tb, with relatively high yield of 149Tb. An efficient radiochemical separation method was developed to separate nca 149–151Tb from bulk praseodymium and coproduced Gd by liquid–liquid extraction (LLX) using aqueous HCl and liquid cation extracting agent di-(2-ethylhexyl)phosphoric acid (HDEHP) dissolved in cyclohexane. Quantitative extraction of nca 149–151Tb was achieved from bulk target with a high separation factor of 4.7×105.

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“…Hence, it has been proposed repeatedly that this goal is best achieved using a single precursor, labeled either with a diagnostic (positron‐ or gamma‐emitting) or a therapeutic (beta‐ and alpha‐emitting) isotope of the same element. Many sets of “matched isotopes” have been suggested for this purpose, eg, 124 I and 131 I, 86 Y and 90 Y, 64 Cu and 67 Cu, 43/44 Sc and 47 Sc, 149 Tb, 152 Tb, 155 Tb, and 161 Tb, but also single nuclides applicable for both modalities due to suitable radiation characteristics, such as 64 Cu offering both β + and β − decay, or 149 Tb which possesses an α‐ and β + branch.…”

Section: Radiometal‐based Thera(g)nostics—a Critical Analysismentioning

confidence: 99%

Re‐thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

Notni

Wester

2017

Labelled Comp Radiopharmac

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The potential and future role of certain metal radionuclides, for example, Sc, Zr, Y, Cu, Ga, Lu, Ac, and Bi, and several terbium isotopes has been controversially discussed in the past decades. Furthermore, the possible benefits of "matched pairs" of isotopes for tandem applications of diagnostics and therapeutics (theranostics) have been emphasized, while such approaches still have not made their way into routine clinical practice. Analysis of bibliographical data illustrates how popularity of certain nuclides has been promoted by cycles of availability and applications. We furthermore discuss the different practical requirements for diagnostic and therapeutic radiopharmaceuticals and the resulting consequences for efficient development of clinically useful pairs of radionuclide theranostics, with particular emphasis on the underlying economical factors. Based on an exemplary assessment of overall production costs for Ga and F radiopharmaceuticals, we venture a look into the future of theranostics and predict that high-throughput PET applications, that is, diagnosis of frequent conditions, will ultimately rely on F tracers. PET radiometals will occupy a niche in the clinical low-throughput sector (diagnosis of rare diseases), but above all, dominate preclinical research and clinical translation. Matched isotope pairs will be of lesser relevance for theranostics but may become important for future PET-based therapeutic dosimetry.

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Production routes of the alpha emitting ¹⁴⁹Tb for medical application

Cited by 63 publications

References 14 publications

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β⁻-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β⁻-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

Investigation on the production and isolation of ^149,150,151Tb from ¹²C irradiated natural praseodymium target

Re‐thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

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Production routes of the alpha emitting 149Tb for medical application

Cited by 63 publications

References 14 publications

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β−-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β−-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

Investigation on the production and isolation of 149,150,151Tb from 12C irradiated natural praseodymium target

Re‐thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals

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Production routes of the alpha emitting ¹⁴⁹Tb for medical application

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β⁻-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

A Unique Matched Quadruplet of Terbium Radioisotopes for PET and SPECT and for α- and β⁻-Radionuclide Therapy: An In Vivo Proof-of-Concept Study with a New Receptor-Targeted Folate Derivative

Investigation on the production and isolation of ^149,150,151Tb from ¹²C irradiated natural praseodymium target