Determination of the RBE of Alpha-Particles from Astatine-211 as Compared to Beta-Particles from Iodine-132 in the Rat Thyroid

Basson, J.K.; Shellabarger, Claire J.

doi:10.2307/3570542

Cited by 15 publications

(2 citation statements)

References 16 publications

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“…The cytotoxic properties of a particle emission of astatine-211 have been known for many years (29,30), as has the potential for tumor-site-selective delivery of different radionuclides by monoclonal antibodies (31)(32)(33). However, coupling of astatine to antibodies for use in radioimmunotherapy has presented a formidable challenge as the chemistry of astatine is not fully understood (34,35).…”

Section: Discussionmentioning

confidence: 99%

Astatine-211 labeling of an antimelanoma antibody and its Fab fragment using N-succinimidyl p-[211At]astatobenzoate: comparisons in vivo with the p-[125I]iodobenzoyl conjugate

Hadley¹,

Wilbur²,

Gray³

et al. 1991

Bioconjugate Chem.

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Astatine-211 labeling of an antimelanoma antibody, NR-ML-05, and its Fab fragment with N-succinimidyl p-[211At]astatobenzoate (2a) has been described. Preparation of the astatinated intermediate 2a was accomplished by distilling astatine-211 from an irradiated bismuth target directly into a reaction mixture containing an organometallic compound, N-succinimidyl p-(tri-n-butylstannyl)benzoate (1), and an oxidant, N-chlorosuccinimide, in 5% HOAc/MeOH. Trapping of distilled astatine as 2a was found to be efficient, resulting in 70-90% yields based on the amount of astatine-211 in the reaction mixture. The dry distillation technique employed gave recoveries of astatine-211 which ranged from 20% to 75%. Conjugation of 2a to NR-ML-05 and its Fab fragment was accomplished in 40-60% yields. The [211At]astatobenzoyl-conjugated antibodies were found to be stable in vitro when challenged by strong denaturants and nucleophilic reagents. Coinjected dual-labeled studies of the 2a astatinated antibodies and the same antibodies labeled with N-succinimidyl p-[125I]iodobenzoate (2b) in athymic mice bearing the human tumor xenograft A375 Met/Mix demonstrated that both radiolabeled antibodies had equivalent tumor localization. Data from the dual-labeled biodistribution of the intact antibody suggests that the astatine is stably attached. Data from the dual-labeled Fab fragment suggests that a portion of the astatine label is released as astatide, either from the astatinated Fab or from a catabolite.

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Section: Discussionmentioning

confidence: 99%

Astatine-211 labeling of an antimelanoma antibody and its Fab fragment using N-succinimidyl p-[211At]astatobenzoate: comparisons in vivo with the p-[125I]iodobenzoyl conjugate

Hadley¹,

Wilbur²,

Gray³

et al. 1991

Bioconjugate Chem.

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“…Relative biological effectiveness (RBE) of a-particles is at least 3-5 • higher compared with c-radiation, is independent of the dose rate and tumor oxygenation. [32][33][34] Using targeted 227 Th-labeled agents, DNA-damaging energy can be deposited selectively in the OST cells and in cells within a close vicinity to the site of decay thereby sparing normal tissues.…”

mentioning

confidence: 99%

Alpha-Particle Therapy for Multifocal Osteosarcoma: A Hypothesis

Baranowska‐Kortylewicz

Sharp

McGuire

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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Osteosarcoma (OST) is the most common bone tumor in children and adolescents with a second peak of incidence in elderly adults usually diagnosed as secondary tumors in Paget's disease or irradiated bone. Subjects with metastatic disease or whose disease relapses after the initial therapy have a poor prognosis. Moreover, multifocal OST contains tumor-initiating cells that are resistant to chemotherapy. The use of aggressive therapies in an attempt to eradicate these cells can have long-term negative consequences in these vulnerable patient populations. 227 Th-labeled molecular probes based on ligands to OST-associated receptors such as IGF-1R (insulin-like growth factor receptor 1), HER2 (human epidermal growth factor receptor 2), and PSMA (prostate-specific membrane antigen) are expected to detect and treat osseous and nonosseous sites of multifocal OST. Published reports indicate that 227 Th has limited myelotoxicity, can be stably chelated to its carriers and, as it decays at targeted sites, 227 Th produces 223 Ra that is subsequently incorporated into the areas of increased osteoblastic activity, that is, osseous metastatic lesions. Linear energy transfer of a particles emitted by 227 Th and its daughter 223 Ra is within the range of the optimum relative biological effectiveness. The radiotoxicity of a particles is virtually independent of the phase in the cell cycle, oxygenation, and the dose rate. For these reasons, even resistant OST cells remain susceptible to killing by high-energy a particles, which can also kill adjacent quiescent OST cells or cells with low expression of targeted receptors. Systemic side effects are minimized by the limited range of these intense radiations. Quantitative single-photon emission computed tomography of 227 Th and 223 Ra is feasible. Additionally, the availability of radionuclide pairs, for example, 89 Zr for positron emission tomography and 227 Th for therapy, establish a strong basis for the theranostic use of 227 Th in the individualized treatment of multifocal OST.

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Preparatton and high pressure liquid chromatography of 5‐astatouracil

Meyer

Rössler

Stöcklin

1976

Labelled Comp Radiopharmac

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SUPBlARY5-astatouracil was prepared via the decomposition of the 5-diazonium salt of uracil in the presence of 'llAt-with overall yields ranging from 20 to 30%.Identification and separation was carried out on four different high pressure liquid chromatography columns. Under identical conditions, astatination is more effective than iodination, and complex formation of halide with the diazonium compound seems to be the product forming mechanism.

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Determination of the RBE of Alpha-Particles from Astatine-211 as Compared to Beta-Particles from Iodine-132 in the Rat Thyroid

Cited by 15 publications

References 16 publications

Astatine-211 labeling of an antimelanoma antibody and its Fab fragment using N-succinimidyl p-[211At]astatobenzoate: comparisons in vivo with the p-[125I]iodobenzoyl conjugate

Astatine-211 labeling of an antimelanoma antibody and its Fab fragment using N-succinimidyl p-[211At]astatobenzoate: comparisons in vivo with the p-[125I]iodobenzoyl conjugate

Alpha-Particle Therapy for Multifocal Osteosarcoma: A Hypothesis

Preparatton and high pressure liquid chromatography of 5‐astatouracil

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