The biological behaviour of some organic astatine compounds in rats

Visser, Gerard W.M.; Diemer, Eduard L.; Vos, C. M. de; Kaspersen, Frans M.

doi:10.1016/0020-708x(81)90078-8

Cited by 28 publications

(10 citation statements)

References 14 publications

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“…However, as another halogen, it may be expected to be absorbed in a proportion close to that of iodine. Injection studies confirm similar behaviour of astatide and iodide, and indicate partial in-vivo deastatination of organic compounds, formation of sulphur-astatine bonds with proteins, and similar tissue distribution for At À , At 0 , and At þ (Visser et al, 1981).…”

Section: Ingestionsupporting

confidence: 52%

See 1 more Smart Citation

ICRP Publication 151: Occupational Intakes of Radionuclides: Part 5

Paquet¹,

Leggett²,

Blanchardon³

et al. 2022

Ann ICRP

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Section: Ingestionsupporting

confidence: 52%

“…Part of bone magnesium exchanges extremely slowly with plasma magnesium. Magnesium residing on bone surfaces is readily released to blood when plasma concentrations decline, but remains bound to bone surfaces at adequate plasma concentrations (Elin, 1987; Vormann, 2003). (62) Aikawa et al.…”

Section: Magnesium (Z = 12)mentioning

confidence: 99%

ICRP Publication 151: Occupational Intakes of Radionuclides: Part 5

Paquet¹,

Leggett²,

Blanchardon³

et al. 2022

Ann ICRP

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“…These are: (i) intravascular therapy with labelled particles, having diameters comparable to that of the capillaries; 25 (ii) radio-immunotherapy with a bifunctional linker 26 for antirenal cell carcinoma, using F(a,b′)2 fragments but not Fab or Fab′ because too high an enrichment in the kidneys was found; 27 (iii) intrathecal injections of rhabdomyosarcoma; 28 (iv) osteosarcoma with TP-3 MOAB; 29 (v) antigastric cancer, 72% tumour inhibition at 20 days; 30 and (vi) metabolic trapping of astinated metabolites: cholesterol, 31 tyrosine, 32 MNDP for rectum adenocarcinoma, 33 MTB for melanoma, 34 MABG for neuroblastoma and phaeochromocytoma, 35 astatotamoxifen for breast cancer, 36 and DNA ligands for rhabdomyosarcoma. 37 To date, only one patient has been treated with At-211. 38 This patient was treated with 200 MBq…”

Section: Alpha-emitting Radio-isotopes Astatine-211mentioning

confidence: 99%

Targeted alpha therapy: Evidence for potential efficacy of alpha-immunoconjugates in the management of micrometastatic cancer

Allen

1999

Australas Radiol

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There can be little doubt that one of the most important problems in the management of cancer is control of metastatic disease. This objective must be achieved ideally with a systemic therapeutic modality that targets cancer cells and gives minimal collateral damage to critical normal cells. The efficacy of targeted cancer therapy relies on the ability of a toxin to be located in the target cancer cell. The ideal toxin is one that is active only in the cancer cell, and not in critical normal cells. Failing this, the next best approach is a toxin with a short effective lifetime to target early stage micrometastatic disease. This rules out chemical toxins, given that they remain effective until excreted from the body, and localization of dose to the cancer cell rules out beta-emitting radio-isotopes (RI). Alpha-emitting RI, however, are much more appropriate toxins because they are short-lived and because their cytotoxicity is the result of their high rate of energy loss and short range of the alpha particles. These radionuclides have properties that are particularly suited for the elimination of single cells in transit or small nests of cancer cells. In vitro and in vivo experiments with alpha RI show dramatic superiority over beta RI. Only a few nuclear hits are needed to kill cells, and the formation of metastatic lung lesions and subcutaneous lesions in mice can be inhibited by systemic administration of alpha emitters. But alpha RI have not been able to control solid tumours, for which beta RI are better suited. A small number of alpha-emitting radionuclides are currently under investigation. These are terbium (Tb)-149, astatine (At)-211, bismuth (Bi)-212 and Bi-213. Terbium-149 and At-211 both require accelerators in close proximity to the place of application. The Bi isotopes are produced by long-lived parents and, as such, can be obtained from generators. The first phase-1 dose escalation trial with Bi-213 radioimmunoconjugate (RIC) commenced in New York in 1997, and other trials are planned with At-211 RIC and At-211 methylene blue for melanoma. Actinium (Ac)-225 is obtained from the decay of thorium (Th)-229, which is a waste product in the enrichment of fissile Th-233. Alternative accelerator production routes are being investigated, beginning with the European Centre for Nuclear Research (CERN) GeV proton spallation source. The ready and low-cost availability of the Ac:Bi generator is an important element in the implementation of clinical trials for patients with poor prognoses but without evidence of metastatic disease.

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“…Since astatine is in the halogen group of elements it was reasoned that its chemistry would parallel radioiodine (7). Early attempts to radiolabel proteins (8,9) and tyrosine (10) with astatine provided evidence that its chemistry was different. Indeed, unlike radioiodine, labeling proteins directly with astatine produced a labile astatine-protein bond, which appeared to be formed from the reaction of astatine with the protein sulfhydryl groups (11).…”

Section: Introductionmentioning

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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The biological behaviour of some organic astatine compounds in rats

Cited by 28 publications

References 14 publications

ICRP Publication 151: Occupational Intakes of Radionuclides: Part 5

ICRP Publication 151: Occupational Intakes of Radionuclides: Part 5

Targeted alpha therapy: Evidence for potential efficacy of alpha-immunoconjugates in the management of micrometastatic cancer

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

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