Auger electron emitter against multiple myeloma — targeted endo-radio-therapy with 125I-labeled thymidine analogue 5-iodo-4′-thio-2′-deoxyuridine

Morgenroth, Agnieszka; Dinger, Cornelia; Zlatopolskiy, Boris D.; Al‐Momani, Ehab; Glatting, Gerhard; Mottaghy, Felix M.; Reske, Sven N.

doi:10.1016/j.nucmedbio.2011.02.018

Cited by 11 publications

(10 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multiple myeloma cell lines KMS12BM, MM1.S, and MM1.R cell lines were shown to contain distinct populations of CD138 À cells that express markers reminiscent of B cells (13,18). A minor cell fraction ranging from 4% to 7% was determined as CD138…”

Section: Isolated Myeloma Cell Populations Resemble Memory B Cells Anmentioning

confidence: 99%

Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma

Morgenroth

Vogg

Zlatopolskiy

et al. 2014

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Isolated Myeloma Cell Populations Resemble Memory B Cells Anmentioning

confidence: 99%

Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma

Morgenroth

Vogg

Zlatopolskiy

et al. 2014

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…Because Auger electrons are characterized by short path lengths in the tissue and a very high linear energy transfer, their cytotoxic effects are limited to a sphere of a few nanometers in the immediate vicinity of the site of decay [2]. This property potentially makes them highly selective for killing targeted single cancer cells, provided that they can be specifically delivered to tumor cells, internalized, and transported to the cell nucleus [3].…”

Section: Introductionmentioning

confidence: 99%

Modular nanotransporters: a versatile approach for enhancing nuclear delivery and cytotoxicity of Auger electron-emitting 125I

et al. 2012

View full text Add to dashboard Cite

BackgroundThis study evaluates the potential utility of a modular nanotransporter (MNT) for enhancing the nuclear delivery and cytotoxicity of the Auger electron emitter 125I in cancer cells that overexpress the epidermal growth factor receptor (EGFR).MethodsMNTs are recombinant multifunctional polypeptides that we have developed for achieving selective delivery of short-range therapeutics into cancer cells. MNTs contain functional modules for receptor binding, internalization, endosomal escape and nuclear translocation, thereby facilitating the transport of drugs from the cell surface to the nucleus. The MNT described herein utilized EGF as the targeting ligand and was labeled with 125I using N-succinimidyl-4-guanidinomethyl-3-[125I]iodobenzoate (SGMIB). Membrane binding, intracellular and nuclear accumulation kinetics, and clonogenic survival assays were performed using the EGFR-expressing A431 epidermoid carcinoma and D247 MG glioma cell lines.Results[125I]SGMIB-MNT bound to A431 and D247 MG cells with an affinity comparable to that of native EGF. More than 60% of internalized [125I]SGMIB-MNT radioactivity accumulated in the cell nuclei after a 1-h incubation. The cytotoxic effectiveness of [125I]SGMIB-MNT compared with 125I-labeled bovine serum albumin control was enhanced by a factor of 60 for D247 MG cells and more than 1,000-fold for A431 cells, which express higher levels of EGFR.ConclusionsMNT can be utilized to deliver 125I into the nuclei of cancer cells overexpressing EGFR, significantly enhancing cytotoxicity. Further evaluation of [125I]SGMIB-MNT as a targeted radiotherapeutic for EGFR-expressing cancer cells appears warranted.

show abstract

“…Considering the small size of SARS-CoV-2 virions (80-120 nm) and the aim to minimize damage to host cells, the most suitable radioactive emitters for this approach would be Auger electron-emitting radionuclides. Due to the relatively low toxicity of these radionuclides when emitted in the cytoplasm or outside of the cell, these radionuclides would need to reach the nucleus to effectively damage the DNA of host cells [142][143][144][145][146][147][148] (Figure 10 bottom). At the same time, Auger electrons with a LET between 0.5 and 10 keV/µm delivered to or into the viral membrane envelope have been estimated to be sufficiently energetic for antiviral effects [107].…”

Section: Radionuclide Therapy Targeting Sars-cov-2 Virionsmentioning

confidence: 99%

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics

2020

Self Cite

View full text Add to dashboard Cite

The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular level and for treatment approaches based on targeted delivery of therapeutic radionuclides. Ongoing development of radiolabeling methods has significantly improved the accessibility of radiopharmaceuticals for in vivo molecular imaging or targeted radionuclide therapy, but their use for biosafety threats such as SARS-CoV-2 is restricted by the contagious nature of these agents. Here, we highlight several potential uses of nuclear medicine in the context of SARS-CoV-2 and COVID-19, many of which could also be performed in laboratories without dedicated containment measures. In addition, we provide a broad overview of experimental or repurposed SARS-CoV-2-targeting drugs and describe how radiolabeled analogs of these compounds could facilitate antiviral drug development and translation to the clinic, reduce the incidence of late-stage failures and possibly provide the basis for radionuclide-based treatment strategies. Based on the continuing threat by emerging coronaviruses and other pathogens, it is anticipated that these applications of nuclear medicine will become a more important part of future antiviral drug development and treatment.

show abstract

Auger electron emitter against multiple myeloma — targeted endo-radio-therapy with 125I-labeled thymidine analogue 5-iodo-4′-thio-2′-deoxyuridine

Cited by 11 publications

References 30 publications

Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma

Breaking the Invulnerability of Cancer Stem Cells: Two-Step Strategy to Kill the Stem-like Cell Subpopulation of Multiple Myeloma

Modular nanotransporters: a versatile approach for enhancing nuclear delivery and cytotoxicity of Auger electron-emitting 125I

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics

Contact Info

Product

Resources

About