Iodine-125-labelled Tamoxifen is Differentially Cytoxic to Cells Containing Oestrogen Receptors

Bloomer, William D.; McLaughlin, William; Weichselbaum, Ralph R.; Tonnesen, Glenn L.; Hellman, Samuel; Seitz, David E.; Hanson, Robert N.; Adelstein, S. James; Rosner, Anthony L.; Burstein, Nelson A.; Nove, John; Jb, Little

doi:10.1080/09553008014551101

Cited by 34 publications

(12 citation statements)

References 23 publications

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“…Therefore, the toxicity of Auger-emitting radionuclides is expected to be quite high and to depend critically on close proximity of the decaying atom to DNA. These predictions have been substantiated by in vitro studies, which have indicated that the decay of Auger-electron emitters covalently bound to nuclear DNA leads to a monoexponential decrease in survival [6,32,35]; the curves may or may not exhibit a shoulder when the decaying atoms are not covalently bound to nuclear DNA [33,36,37]; and, in general, intranuclear decay accumulation is highly toxic (D 0 ∼ 100 -500 decays/cell), whereas decay within the cytoplasm or extracellularly produces no extraordinary lethal effects and these survival curves resemble those observed with X-ray (have a distinct shoulder) [33,38].…”

Section: Nonenergetic Particlesmentioning

confidence: 84%

Radiotargeting agents for cancer therapy

Kassis¹

2005

Expert Opinion on Drug Delivery

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Although the general radiobiological principles underlying external beam therapy and radionuclide therapy are the same, there are significant differences in the radiobiological effects observed in mammalian cells. In external beam therapy and brachytherapy, emissions are composed of photons, whereas in radionuclide therapy, the radiations of interest are particulate. This article will explore the special features that characterise the biological effects consequent to the traversal of charged particles through mammalian cells. In addition, it will highlight what has been learned when these radionuclides and targeting radiopharmaceuticals are used to treat cancers.

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Section: Nonenergetic Particlesmentioning

confidence: 84%

Radiotargeting agents for cancer therapy

Kassis¹

2005

Expert Opinion on Drug Delivery

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“…The D37 for x-rays is considered to be about 580 rads. When ~ZSl was only sequestered near DNA, the D37 was 0.5 pCi/cell [281] and when able to freely diffuse in and out of mammalian cells (not bound to any cellular macromolecule), ~25I was still I0-11 times more lethal than external radiation 1282].…”

Section: Documented Effects Of Tissue-incorporated Auger Electron Emimentioning

confidence: 99%

Cancer risk from inorganics

Swierenga¹,

Gilman

McLean

1987

Cancer Metast Rev

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Inorganic metals and minerals for which there is evidence of carcinogenicity are identified. The risk of cancer from contact with them in the work place, the general environment, and under conditions of clinical (medical) exposure is discussed. The evidence indicates that minerals and metals most often influence cancer development through their action as cocarcinogens. The relationship between the physical form of mineral fibers, smoking and carcinogenic risk is emphasized. Metals are categorized as established (As, Be, Cr, Ni), suspected (Cd, Pb) and possible carcinogens (Table 6), based on the existing in vitro, animal experimental and human epidemiological data. Cancer risk and possible modes of action of elements in each class are discussed. Views on mechanisms that may be responsible for the carcinogenicity of metals are updated and analysed. Some specific examples of cancer risks associated with the clinical use of potentially carcinogenic metals and from radioactive pharmaceuticals used in therapy and diagnosis are presented. Questions are raised as to the effectiveness of conventional dosimetry in accurately measuring risk from radiopharmaceuticals.

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“…This approach is an extension of the early use of specific nuclear receptors to target 125 I-tamoxifen (Bloomer et al 1980), or 125 I-triiodothyronine (Sundell-Bergman & Johanson 1982) to the DNA of certain tumor cells.…”

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confidence: 99%

Strand breakage by decay of DNA-bound ¹²⁴I provides a basis for combined PET imaging and Auger endoradiotherapy

Lobachevsky

Clark

Pytel

et al. 2016

International Journal of Radiation Biology

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Purpose DNA ligands labelled with I induce cytotoxic DNA double-strand breaks (DSB), suggesting a potential for Auger endoradiotherapy. Since the 60-day half-life ofI is suboptimal for therapy, we have investigated another Auger-emitter I, with shorter half-life (4.18 days), and the additional feature of positron-emission, enabling positron emission tomography (PET) imaging. The purpose of this study was to compare the two radionuclides on the basis of DNA DSB per decay. Materials and methods Using aI- (or I)-labelled minor groove binding DNA ligand, we investigated DNA breakage using the plasmid DNA assay. Biodistribution of the conjugate of the labelled ligand with transferrin was investigated in nude mice bearing a K562 human lymphoma xenograft. Results The probability of DSB per decay was 0.58 and 0.85 forI and I, respectively, confirming the therapeutic potential of the former. The crystal structure of the ligand DNA complex shows the iodine atom deep within the minor groove, consistent with the high efficiency of induced damage. Biodistribution studies, including PET imaging, showed distinctive results for the conjugate, compared to the free ligand and transferrin, consistent with receptor-mediated delivery of the ligand. Conclusions Conjugation ofI-labelled DNA ligands to tumor targeting peptides provides a feasible strategy for Auger endoradiotherapy, with the advantage of monitoring tumor targeting by PET imaging.

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Iodine-125-labelled Tamoxifen is Differentially Cytoxic to Cells Containing Oestrogen Receptors

Cited by 34 publications

References 23 publications

Radiotargeting agents for cancer therapy

Radiotargeting agents for cancer therapy

Cancer risk from inorganics

Strand breakage by decay of DNA-bound ¹²⁴I provides a basis for combined PET imaging and Auger endoradiotherapy

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Iodine-125-labelled Tamoxifen is Differentially Cytoxic to Cells Containing Oestrogen Receptors

Cited by 34 publications

References 23 publications

Radiotargeting agents for cancer therapy

Radiotargeting agents for cancer therapy

Cancer risk from inorganics

Strand breakage by decay of DNA-bound 124I provides a basis for combined PET imaging and Auger endoradiotherapy

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Product

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About

Strand breakage by decay of DNA-bound ¹²⁴I provides a basis for combined PET imaging and Auger endoradiotherapy