Modeling Dose Deposition and DNA Damage Due to Low-Energy β<sup>–</sup>Emitters

Alloni, D.; Cutaia, C.; Mariotti, Luca; Friedland, W.; Ottolenghi, A.

doi:10.1667/rr13664.1

Cited by 20 publications

(9 citation statements)

References 191 publications

(288 reference statements)

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“…It indicated that the characteristic LDR irradiation of internal radiotherapy demonstrated a definite dose-effect relationship for small lesions and micro-metastatic foci of HCC (Kassis and Adelstein, 2005;Lambert and Van de Wiele, 2005;Goldenberg and Sharkey, 2006). As demonstrated by the results of in vitro experiments, during an irradiation dose range of 2-10 Gy, LDR irradiation could induce marked cell apoptosis and suppress tumor growth (Sgouros, 2005;Alloni et al, 2014). An injection of 131 I-hepama-1 mAb via hepatic artery plus ligation of hepatic artery could lower AFP by 52% and shrink tumor by 78% (Zeng et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

“…The emission is continuous and decreases exponentially. For non-uniformly distributed low dosage rate (LDR) , the biological effects (Juweid et al, 1997;Kassis and Adelstein, 2005;Alloni et al, 2014) of radiation are mainly manifested as non-fatal injury of cellular DNA and an induction of apoptosis and proliferative mortality. And the magnitude of this effect is closely correlated with the targeting of radionuclide.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

¹³¹I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

Wang²

2015

Asian Pacific Journal of Cancer Prevention

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Objective: This study evaluated the safety and objective response of combining 131 I-labeled-metuximab (Licartin) with transarterial chemoembolization (TACE) in the treatment of unresectable hepatocellular carcinoma (HCC). Materials and Methods: In a multicenter open-label clinical trial, 341 enrolled patients with stage III/IV HCC according to TNM criteria were nonrandomly assigned to a trial group (n=167) and a control group (n=174), undergoing TACE following hepatic intra-arterial injection of licartin or TACE alone from July 2007 to July 2009. Radiopharmaceutical distribution was evaluated. The primary endpoint was overall survival; secondary endpoints included time-to-progression (TTP), toxicity and adverse events (AEs). Results: The radiobiological distribution demonstrated better localization of licartin in liver tumors than other tissues (P<0.01). The organ absorbed doses to liver and red marrow were 3.19±1.01 Gy and 0.55±0.22 Gy, respectively. The 1-year survival rate was significantly higher [79.47% vs. 65.59%, hazard ratio (HR), 0.598, P=0.041] and TTP significantly improved (6.82±1.28 vs. 4.7±1.14 months, P=0.037) compared with the control group. Patients at stage III achieved more benefit of one year survival than stage IV in the trial group (86.9% vs. 53.8%, P<0.001). There were significant different toxicities in leukocytopenia, thrombocytopenia and increased total bilirubin level [P<0.001, P=0.013, P<0.01, relative risk (RR) 1.63, 1.33, 1.43], but no differences in severe AEs of upper GI hemorrhage and severe liver dysfunction between the groups (5.39% vs. 2.3%, P=0.136). Conclusions: Owing to excellent tumor-targeting, promised efficacy and favourable toxicity profile, the novel combination therapy of licartin and TACE could be applied in patients with unresectable HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

¹³¹I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

Wang²

2015

Asian Pacific Journal of Cancer Prevention

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“…Indeed, in an apparent paradox, the risk of damage increases when the energy emitted decreases since, when using radionuclides that incorporate into the DNA most of the energy is locally deposited into the nucleus by low-energy compounds, such as tritium 1 2 . Given its low disintegration energy, tritium’s biological effects do not occur from external exposure but from integration of organically bound tritium (OBT) into tissue 3 . In a previous study using labeled nucleoside [ 3 H]thymidine, which is incorporated into DNA, we established a model to analyze the genetic impact of endogenous self-irradiation of DNA by a low energy-emitting source, such as tritium.…”

mentioning

confidence: 99%

A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis

Saintigny

Chevalier

Bravard

et al. 2016

Sci Rep

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Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [3H]thymidine into CHO cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [3H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC > CG and AT > CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses.

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“…Fractionated exposure (to 10 mGy or 100 mGy) resulted in persistent DNA damage in spermatogonia stem cells of mice and also in lung, breast and brain cells [82] [ 85,86] Low-energy β(-) emitters were studied as well [95]. In this way, PARTRAC contributed to new models for radiation-induced cancers.…”

Section: Dose and Dose-rate Dependenciesmentioning

confidence: 99%

Progress in low dose health risk research

Averbeck

Salomaa

Bouffler

et al. 2018

Mutation Research/Reviews in Mutation Research

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People are more often exposed to low as opposed to high doses of ionising radiation (IR). Knowledge on the health risks associated with exposures to ionising radiation above 100 mGy is quite well established, while lower dose risks are inferred from higher level exposure information (ICRP). The health risk assessments are mainly based on epidemiological data derived from the atomic bombing of Hiroshima and Nagasaki, medical exposure studies and follow-up studies after nuclear accidents. For the estimation of long-term stochastic radiation health effects (such as cancer) and radiation protection purposes, a linear non-threshold (LNT) model is applied. However, the general validity of the LNT hypothesis for extrapolations from effects of high to low doses (<100 mGy) and low dose-rates (<6 mGy/h) has been questioned as epidemiological studies are statistically limited at low doses and unable to evaluate low dose and low dose-rate health risks (UNSCEAR). Thus, uncertainties on health risks need to be clarified with the help of mechanistic studies. The European Network of Excellence DoReMi (2010-2016) was designed to address some of the existing uncertainties and to identify research lines that are likely to be most informative for low dose risk assessment. The present review reports the results obtained from studies addressing the induction of cancer and non-cancer effects by low dose IR as well as on individual radiation sensitivity. It is shown that low dose and low dose-rate effects are the result of complex network responses including genetic, epigenetic, metabolic and immunological regulation. Evidence is provided for the existence of nonlinear biological responses in the low and medium dose range as well as effects other than the classical DNA damage. Such effects may have a bearing on the quantitative and qualitative judgements on health effects induced by low dose radiations.

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Modeling Dose Deposition and DNA Damage Due to Low-Energy β^–Emitters

Cited by 20 publications

References 191 publications

¹³¹I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

¹³¹I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis

Progress in low dose health risk research

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Modeling Dose Deposition and DNA Damage Due to Low-Energy β–Emitters

Cited by 20 publications

References 191 publications

131I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

131I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis

Progress in low dose health risk research

Contact Info

Product

Resources

About

Modeling Dose Deposition and DNA Damage Due to Low-Energy β^–Emitters

¹³¹I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study

¹³¹I-Labeled-Metuximab Plus Transarterial Chemoembolization in Combination Therapy for Unresectable Hepatocellular Carcinoma: Results from a Multicenter Phase IV Clinical Study