Production and dosimetric aspects of the potent Auger emitter <sup>58m</sup>Co for targeted radionuclide therapy of small tumors

Thisgaard, Helge; Elema, Dennis Ringkjøbing; Jensen, Mikael

doi:10.1118/1.3608905

Cited by 21 publications

(34 citation statements)

References 28 publications

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“…If such studies become successful, then translation to clinical applications should be feasible. We recently calculated that it will be possible to produce more than 120 GBq of 58m Co in 3 h with a small PET cyclotron (19). Hence, clinical applications with, for example, the administration of 18.5 GBq per patient-as in a study using 111 In-DTPAoctreotide (20)-should be achievable with 58m Co-DOTATATE.…”

Section: Discussionmentioning

confidence: 99%

“…From the published theoretic radiation doses to the cell nucleus (and, thus, the DNA) per decay from the radionuclides used in the present study (i.e., the cellular S values (absorbed dose per unit cumulated activity) (18,19)), it can be calculated that 58m Co delivers approximately 2 and 6 times higher doses to the nucleus for decays taking place in the nucleus and the cytoplasm, respectively, than 111 In. (The corresponding doses are approximately 2 and 11 times higher, respectively, for 58m Co than for 58g Co.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

et al. 2014

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The somatostatin receptor, which is overexpressed by many neuroendocrine tumors, is a well-known target for molecular imaging and peptide receptor radionuclide therapy. Recently, 57 Co-labeled DOTA-TOC, an octreotide analog, was shown to have the highest affinity yet found for somatostatin receptor subtype 2. The aim of this study was to evaluate the biologic effects of novel cobalt-labeled octreotide analogs targeting the somatostatin receptor to identify promising candidates for molecular imaging and Auger electron-based radionuclide therapy. Methods: Cobalt-labeled DOTATATE, DOTATOC, and DOTANOC were prepared with 57 Co or 58m Co for SPECT or Auger electron-based therapy, respectively. The cellular uptake and intracellular distribution of the radioligands were characterized with the pancreatic tumor cell line AR42J in vitro, including assessment of the therapeutic effects of 58m Co-DOTATATE via DNA double-strand break and proliferation assays. Comparisons with the therapeutic effects of 111 In-and 177 Lu-DOTATATE were also performed. Tumor uptake and normal tissue uptake were characterized in a subcutaneous pancreatic tumor mouse model. Results: All 3 cobalt-conjugated peptides resulted in time-dependent and receptor-specific uptake, with a high level (≥88%) of cellular internalization in vitro of the total cell-associated radioactivity. The DNA double-strand break yield showed a dose-dependent increase with activity, whereas cell survival showed a dose-dependent decrease. 58m Co-DOTATATE was significantly more efficient in cell killing per cumulated decay than 111 In-and 177 Lu-DOTATATE. The in vivo pharmacokinetic studies showed a high level of receptor-specific tumor uptake. Conclusion: All cobalt-labeled radioligands showed a high level of receptor-specific uptake both in vitro and in vivo in tumorbearing mice. Furthermore, 58m Co-DOTATATE showed considerable therapeutic effects in vitro and, thus, could be an effective agent for eradicating disseminated tumor cells and micrometastases. Thesomat ostatin receptor, which is overexpressed by many neuroendocrine tumors, is a well-known target for molecular imaging (i.e., PET and SPECT) and for peptide receptor radionuclide therapy (1,2). One of the most widely used radiopharmaceuticals for SPECT imaging of these tumors is 111 In-diethylenetriaminepentaacetic acid ( Recently, 57 Co-labeled DOTATOC was shown to have the highest affinity yet found for the somatostatin receptor subtype 2 (SSTR2) (6). Furthermore, the rate of internalization of this compound into the pancreatic tumor cell line AR42J was the highest found for any somatostatin-based radioligand. In a study by Uusijärvi et al. (7) of 59 therapeutic radionuclides (a, b, and Auger electron emitters), the Auger electron emitter 58m Co was the radionuclide that resulted in the second highest theoretic tumor-to-normal tissue dose rate ratio. Therefore, the therapeutic potency of the 58m Co radionuclide and the remarkable obtainable internalization rates and affinities for SSTR2-expressing tumor cells mak...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

et al. 2014

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“…Production yields of 58m Co and 58g Co from 57 Fe(d,n) were quantified via two methods: 1) indirectly via quantification of 58g Co activity over time (E γ = 811 keV) using an efficiency-calibrated HPGe detector, fitting the data points with the Bateman equation that contains the initial activities of the parent and daugher radionuclides, as it was done by Thisgaard et al [12]; and 2) via direct quantification of 58m Co (E γ = 24.9 keV) using an efficiencycalibrated low-energy HPGe detector as it was done by Sudár and Qaim [22]. The sample employed for this purpose was the 10 µL aliquot drawn from the 3.1 mL target dissolution.…”

Section: M Co and 58g Co Yields And Radionuclidic Impuritiesmentioning

confidence: 99%

“…The therapeutic potential of 58m Co has been recognized theoretically [10][11][12] and experimentally [13]. Experimentally, Thisgaard et al demonstrated that 58m Co-DOTATATE was significantly more efficient in cell killing per cumulated decay than 111 In-and 177 Lu-DOTATATE after exposing pancreatic tumor cells AR42J in vitro [13].…”

Section: Introductionmentioning

confidence: 99%

Auger electron-based targeted radioimmunotherapy with 58mCo, a feasibility study

Valdovinos

Hernandez

Goel

et al. 2016

AIP Conference Proceedings

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Abstract. Co-58m (t 1/2 =9.10 h, 100% IC) is an attractive radionuclide for localized delivery of radiation dose due to its emission of Auger and conversion electrons with high LET in water (2-18 keV/µm). 58mCo decays to a positron-emitting daughter, 58g Co (t 1/2 =70.86 d, 14.9% β + ), which can be readily detected by Positron Emission Tomography (PET) and hence can be employed to verify the biodistribution of the parent isotope post-treatment in vivo. In this work, we describe 1) the targetry and radiochemistry involved in the production of high specific activity 58m Co; and 2) the results of a pilot radiotherapy study using a Co with a separation efficiency of 96±2% and a specific activity with NOTA of 25±6 GBq/µmol. We have produced ~640 MBq of 58m Co-NOTA-TRC105, with a specific activity of 1.2 MBq/µg, in 800 µL of PBS ready for targeted radioimmunotherapy, which we employed in a group of 4 mice. Post-therapy biodistribution was quantified in vivo via PET imaging of the daughter 58g Co.

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“…Indeed, cyclotrons find applications in medicine, where production of therapeutic quantities of Auger emitter from several different isotopes is important in targeted radionuclide therapy of small tumors. 16,17 Modern cyclotrons developments are concerned to the production of the standard isotopes and also new therapeutic isotopes. 18 Applications of cyclotron accelerators include also technological processes, as ion beam lithography.…”

Section: Introductionmentioning

confidence: 99%

Scaling investigation for the dynamics of charged particles in an electric field accelerator

Ladeira¹,

Leonel

2012

Chaos: An Interdisciplinary Journal of Nonlinear Science

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Some dynamical properties of an ensemble of trajectories of individual (non-interacting) classical particles of mass m and charge q interacting with a time-dependent electric field and suffering the action of a constant magnetic field are studied. Depending on both the amplitude of oscillation of the electric field and the intensity of the magnetic field, the phase space of the model can either exhibit: (i) regular behavior or (ii) a mixed structure, with periodic islands of regular motion, chaotic seas characterized by positive Lyapunov exponents, and invariant Kolmogorov-Arnold-Moser curves preventing the particle to reach unbounded energy. We define an escape window in the chaotic sea and study the transport properties for chaotic orbits along the phase space by the use of scaling formalism. Our results show that the escape distribution and the survival probability obey homogeneous functions characterized by critical exponents and present universal behavior under appropriate scaling transformations. We show the survival probability decays exponentially for small iterations changing to a slower power law decay for large time, therefore, characterizing clearly the effects of stickiness of the islands and invariant tori. For the range of parameters used, our results show that the crossover from fast to slow decay obeys a power law and the behavior of survival orbits is scaling invariant. The formalism of escape is used to study the dynamics and hence the transport of charged particles in an accelerator. The model consists of a periodically time dependent electric field limited to a certain region in space that furnishes or absorbs energy of a particle. After the particle leaves the electric field region, a constant magnetic field impels the particle to move in a circular trajectory. This magnetic field is responsible for bringing the particle back to the electric field region leaving the energy unchanged. The control parameters e and s represent the amplitude of the time-dependent electric field and the inverse of the magnetic field, respectively. The parameter e defines the nonlinear strength while ps defines the time that the particle spends in the magnetic region. The dynamics can be described by a two-dimensional nonlinear mapping. Depending on both e and s, the phase space presents either regular or mixed structure. For e ¼ 0, the nonlinear term vanishes and the particle's energy is constant in time. For s ¼ 1; 3; 5; …, there is a strong correlation between the frequency of oscillation of the electric field and the intensity of the magnetic field, and as a consequence, the motion of the particle is regular. For different control parameters than those discussed, the phase space presents mixed structure with islands of regular motion surrounded by chaotic seas and invariant KAM curves that prevent the particle from acquiring unbounded energy gain. We study the escape of particles through a hole in the phase space placed in the velocity axis by considering the position of the lowest energy KAM curve. An ensemb...

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Production and dosimetric aspects of the potent Auger emitter ^58mCo for targeted radionuclide therapy of small tumors

Cited by 21 publications

References 28 publications

Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

Auger electron-based targeted radioimmunotherapy with 58mCo, a feasibility study

Scaling investigation for the dynamics of charged particles in an electric field accelerator

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Production and dosimetric aspects of the potent Auger emitter 58mCo for targeted radionuclide therapy of small tumors

Cited by 21 publications

References 28 publications

Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron–Based Radionuclide Therapy

Auger electron-based targeted radioimmunotherapy with 58mCo, a feasibility study

Scaling investigation for the dynamics of charged particles in an electric field accelerator

Contact Info

Product

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Production and dosimetric aspects of the potent Auger emitter ^58mCo for targeted radionuclide therapy of small tumors