Investigating intrinsic radiosensitivity biomarkers to peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE in a panel of cancer cell lines

Delbart, Wendy; Ghanem, Ghanem E.; Karfis, Ioannis; Flamen, Patrick; Wimana, Zéna

doi:10.1016/j.nucmedbio.2021.03.006

Cited by 7 publications

(18 citation statements)

References 65 publications

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Section: Resultsmentioning

confidence: 99%

“…The radiosensitivity to 177 Lu-DOTATATE and EBRT of the panel of human cancer cell lines (melanoma, multiple myeloma and gastroenteropancreatic (GEP) carcinoma) was evaluated, using a previously published treatment schedule for 177 Lu-DOTATATE [ 9 , 10 ] and the clinically applied 2 Gy dose of EBRT [ 11 , 12 ]. The effect of 177 Lu-DOTATATE on the survival of the six human cancer cell lines expressing SSTRs as a function of time was described in our previous work [ 9 ]. The multiple myeloma cell lines COLO-677 and EJM and the melanoma cell line HBL were the most radiosensitive, with a significant cell survival reduction at day 10 of 33% ± 2%, 22% ± 2% and 26% ± 4%, respectively (all p values < 0.001).…”

Section: Resultsmentioning

confidence: 99%

“…The modest biological effects reported in 177 Lu-DOTATATE-treated cells may also be due to the low internalized fraction in our study. Conversely, the U2OS SSTR2 , an SSTR-negative human osteosarcoma cell line transfected to stably express SSTR2 [ 34 ], had a 250 times higher internalized fraction (250 mBq/cell) compared to our HBL cell line (1 mBq/cell in [ 9 ]) after 2 h incubation with 177 Lu-DOTATATE (in both cases). This resulted in a minor contribution of the internalized fraction to the total absorbed dose.…”

Section: Discussionmentioning

confidence: 99%

“…Cell line authentication was performed with a short tandem repeat (STR) test (Eurofins Genomics, Germany). Cell lines were chosen based on two characteristics: (i) cell lines derived from malignancies expressing SSTRs in order to ensure the presence of the target [ 9 ] and (ii) cell lines derived from malignancies exhibiting a range of intrinsic radiosensitivities (from radiosensitive (myeloma) to radioresistant (melanoma) and intermediate radiosensitivity (pancreatic and colorectal cancers), classified as such based on the mean survival at 2 Gy of EBRT [ 39 ]).…”

Section: Methodsmentioning

confidence: 99%

“…Cells were seeded in 12-well plates (Corning ® CellBIND ® Multiple Well Plate, Merck) at different densities according to the time point evaluated ( Table A1 ). The next day (corresponding to day 0), cells were irradiated, either with 177 Lu-DOTATATE as previously described [ 9 ] or with EBRT.…”

Section: Methodsmentioning

confidence: 99%

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Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy

Delbart

Karabet

Marin

et al. 2022

IJMS

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Radionuclide Therapy (RNT) with 177Lu-DOTATATE targeting somatostatin receptors (SSTRs) in neuroendocrine tumours (NET) has been successfully used in routine clinical practice, mainly leading to stable disease. Radiobiology holds promise for RNT improvement but is often extrapolated from external beam radiation therapy (EBRT) studies despite differences in these two radiation-based treatment modalities. In a panel of six human cancer cell lines expressing SSTRs, common radiobiological endpoints (i.e., cell survival, cell cycle, cell death, oxidative stress and DNA damage) were evaluated over time in 177Lu-DOTATATE- and EBRT-treated cells, as well as the radiosensitizing potential of poly (ADP-ribose) polymerase inhibition (PARPi). Our study showed that common radiobiological mechanisms were induced by both 177Lu-DOTATATE and EBRT, but to a different extent and/or with variable kinetics, including in the DNA damage response. A higher radiosensitizing potential of PARPi was observed for EBRT compared to 177Lu-DOTATATE. Our data reinforce the need for dedicated RNT radiobiology studies, in order to derive its maximum therapeutic benefit.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy

Delbart

Karabet

Marin

et al. 2022

IJMS

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Application of peptide biomarkers in life analysis based on liquid chromatography–mass spectrometry technology

Han

Cong

et al. 2022

BioFactors

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Biomedicine is developing rapidly in the 21st century. Among them, the qualitative and quantitative analysis of peptide biomarkers is of considerable importance for the diagnosis and therapy of diseases and the quality evaluation of drugs and food. The identification and quantitative analysis of peptides have been going on for decades. Traditionally, immunoassays or biological assays are generally used to quantify peptides in biological matrices. However, the selectivity and sensitivity of these methods cannot meet the requirements of the application. The separation and analysis technique of liquid chromatography-mass spectrometry (LC-MS) supplies a reliable alternative. In contrast to immunoassays, LC-MS methods are capable of providing the analytical prowess necessary to satisfy the demands of peptide biomarker research in the life sciences arena. This review article provides a historical account of the in-roads made by LC-MS technology for the detection of peptide biomarkers in the past 10 years, with the focus on the qualification/quantification developments and their applications.

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Molecular Radiation Biology

Reindl,

Abrantes,

Ahire

et al. 2023

Radiobiology Textbook

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Various exogeneous and endogenous factors constantly cause damages in the biomolecules within a cell. For example, per day, 10,000–100,000 molecular lesions occur in DNA per cell. The molecule modifications that are formed disturb the structure and function of the affected molecules. The purpose of this chapter is to introduce the damages to biomolecules caused by radiation, the associated repair pathways, and the effect on the cellular function. Special interest lies on the damages induced to DNA, the carrier of the human genome, and the consequence to genomic integrity, cell death, and cell survival. Additionally, related effects regarding inflammation and immunity, epigenetic factors, and omics are discussed. The chapter concludes with an explanation of the molecular factors of cellular hyper-radiosensitivity and induced radiation resistance.

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Investigating intrinsic radiosensitivity biomarkers to peptide receptor radionuclide therapy with [177Lu]Lu-DOTATATE in a panel of cancer cell lines

Cited by 7 publications

References 65 publications

Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy

Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy

Application of peptide biomarkers in life analysis based on liquid chromatography–mass spectrometry technology

Molecular Radiation Biology

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