Cytotoxic and genotoxic effect of the [166Dy]Dy/166Ho-EDTMP in vivo generator system in mice

Pedraza-López, Martha; Ferro-Flores, Guillermina; Murphy, Consuelo Arteaga de; Morales-Ramı́rez, P.; Piedras-Ross, Josefa; Murphy-Stack, Eduardo; Hernandez-Oviedo, O.

doi:10.1016/j.nucmedbio.2004.08.010

Cited by 12 publications

(6 citation statements)

References 10 publications

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“…Micronuclei and chromosomal assays were frequently used for the detection and assessment of cytotoxic and genotoxic damage induced by mutagens and environmental pollutants, including heavy metals in mammalian (Heddle et al 1983;Fenech and Morley 1985) and plant cells (Degrassi and Rizzoni 1982;Ma et al 1995;Steinkellner et al 1998;Qian 2004). Our results confirmed chromosomal abnormalities previously described after Cr exposure (see "Introduction") and indicated that micronuclei appeared after long treatments [100 μΜ Cr(VI), 48 and 72 h].…”

Section: Cr(vi) Effects On Mts and Er Distributionsupporting

confidence: 87%

Effects of hexavalent chromium on microtubule organization, ER distribution and callose deposition in root tip cells of Allium cepa L.

2011

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The subcellular targets of hexavalent chromium [Cr(VI)] were examined in Allium cepa root tips with confocal laser scanning microscopy. Cr(VI) exerted dose- and time-dependent negative effects on root growth rate, the mitotic index and microtubule (MT) organization during cell division cycle. Interphase MTs were more resistant than the mitotic ones, but when affected they were shorter, sparse and disoriented. The preprophase band of MTs became poorly organized, branched or with fragmented MTs, whilst neither a perinuclear array nor a prophase spindle was formed. Metaphase spindles converged to eccentric mini poles or consisted of dissimilar halves and were unable to correctly orient the chromosomes. Anaphase spindles were less disturbed, but chromatids failed to separate; neither did they move to the poles. At telophase, projecting, lagging or bridging chromosomes and micronuclei also occurred. Phragmoplasts were unilaterally developed, split, located at unexpected sites and frequently dissociated from the branched and misaligned cell plates. Chromosomal aberrations were directly correlated with MT disturbance. The morphology and distribution of endoplasmic reticulum was severely perturbed and presumably contributed to MT disassembly. Heavy callose apposition was also induced by Cr(VI), maybe in the context of a cellular defence reaction. Results indicate that MTs are one of the main subcellular targets of Cr(VI), MT impairment underlies chromosomal and mitotic aberrations, and MTs may constitute a reliable biomonitoring system for Cr(VI) toxicity in plants.

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Section: Cr(vi) Effects On Mts and Er Distributionsupporting

confidence: 87%

Effects of hexavalent chromium on microtubule organization, ER distribution and callose deposition in root tip cells of Allium cepa L.

2011

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“…Theoretical bone marrow absorbed dose calculations indicate that the [ 166 Dy]Dy/[ 166 Ho]Ho EDTMP in vivo generator system produced 3.47 times more dose than [ 166 Ho]Ho DOTMP per unit of initial activity in the skeleton (Pedraza-Lopez et al 2004a). The same group also demonstrated that the [ 166 Dy]Dy/[ 166 Ho]Ho EDTMP system induced considerable cytotoxicity, genotoxicity and severe myelosuppression in mice at bone marrow absorbed doses of 18–23 Gy, suggesting that this system could potentially be a good agent for use in humans (Pedraza-Lopez et al 2004b).…”

Section: Intravenous Applicationsmentioning

confidence: 98%

The various therapeutic applications of the medical isotope holmium-166: a narrative review

Klaassen¹,

Arntz²,

Arranja

et al. 2019

EJNMMI radiopharm. chem.

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Over the years, a broad spectrum of applications of the radionuclide holmium-166 as a medical isotope has been established. The isotope holmium-166 is attractive as it emits high-energy beta radiation which can be used for a therapeutic effect and gamma radiation which can be used for nuclear imaging purposes. Furthermore, holmium-165 can be visualized by MRI because of its paramagnetic properties and by CT because of its high density. Since holmium-165 has a natural abundance of 100%, the only by-product is metastable holmium-166 and no costly chemical purification steps are necessary for production of nuclear reactor derived holmium-166. Several compounds labelled with holmium-166 are now used in patients, such Ho 166 -labelled microspheres for liver malignancies, Ho 166 -labelled chitosan for hepatocellular carcinoma (HCC) and [ 166 Ho]Ho DOTMP for bone metastases. The outcomes in patients are very promising, making this isotope more and more interesting for applications in interventional oncology. Both drugs as well as medical devices labelled with radioactive holmium are used for internal radiotherapy. One of the treatment possibilities is direct intratumoural treatment, in which the radioactive compound is injected with a needle directly into the tumour. Numerous other applications have been developed, like patches for treatment of skin cancer and holmium labelled antibodies and peptides. The second major application that is currently clinically applied is selective internal radiation therapy (SIRT, also called radioembolization), a novel treatment option for liver malignancies. This review discusses medical drugs and medical devices based on the therapeutic radionuclide holmium-166.

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“…This remains true of the complex following decay to the Ho ( t 1/2 = 26.6 h) daughter [57]. When complexed with ethylenediaminetetramethylene phosphonate (EDTMP) 166 Dy has been shown to accumulate in skeletal tissue and therefore can be applied for marrow ablation [58]. …”

Section: Therapeutic In Vivo Generatorsmentioning

confidence: 99%

In Vivo Radionuclide Generators for Diagnostics and Therapy

Edem

Fonslet

Kjær

et al. 2016

Bioinorganic Chemistry and Applications

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In vivo radionuclide generators make complex combinations of physical and chemical properties available for medical diagnostics and therapy. Perhaps the best-known in vivo generator is 212Pb/212Bi, which takes advantage of the extended half-life of 212Pb to execute a targeted delivery of the therapeutic short-lived α-emitter 212Bi. Often, as in the case of 81Rb/81Kr, chemical changes resulting from the transmutation of the parent are relied upon for diagnostic value. In other instances such as with extended alpha decay chains, chemical changes may lead to unwanted consequences. This article reviews some common and not-so-common in vivo generators with the purpose of understanding their value in medicine and medical research. This is currently relevant in light of a recent push for alpha emitters in targeted therapies, which often come with extended decay chains.

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Cytotoxic and genotoxic effect of the [166Dy]Dy/166Ho-EDTMP in vivo generator system in mice

Cited by 12 publications

References 10 publications

Effects of hexavalent chromium on microtubule organization, ER distribution and callose deposition in root tip cells of Allium cepa L.

Effects of hexavalent chromium on microtubule organization, ER distribution and callose deposition in root tip cells of Allium cepa L.

The various therapeutic applications of the medical isotope holmium-166: a narrative review

In Vivo Radionuclide Generators for Diagnostics and Therapy

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