Future Vistas in Alpha Therapy of Infectious Diseases

Dadachova, Ekaterina

doi:10.1016/j.jmir.2019.06.052

Cited by 8 publications

(6 citation statements)

References 30 publications

(31 reference statements)

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“…Since the Food and Drug Administration (FDA) approval of radium-223 dichloride ([ 223 Ra]RaCl 2 , Xofigo, Bayer) in 2013 [12], both the pre-clinical and clinical potential of α-particles-with a focus on the management of metastatic cancer diseases-has been fiercely investigated. The research is not restricted to cancer management alone but also covers the treatment of HIV as well as fungal and bacterial infections with promising results (for a review, see [13,14]). α-particles are generally considered to be highly promising due to their characteristics-the short particle range in tissue (40-100 µm or 2-10 cell diameters) and high-linear energy transfer (LET; ≈80 keV/µm)-which result in a high cytocidal effect for malignant tissue while sparing healthy surrounding tissue [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

2020

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Atomic in vivo nanogenerators such as actinium-225, thorium-227, and radium-223 are of increasing interest and importance in the treatment of patients with metastatic cancer diseases. This is due to their peculiar physical, chemical, and biological characteristics, leading to astonishing responses in otherwise resistant patients. Nevertheless, there are still a few obstacles and hurdles to be overcome that hamper the broader utilization in the clinical setting. Next to the limited supply and relatively high costs, the in vivo complex stability and the fate of the recoiling daughter radionuclides are substantial problems that need to be solved. In radiobiology, the mechanisms underlying treatment efficiency, possible resistance mechanisms, and late side effect occurrence are still far from being understood and need to be unraveled. In this review, the current knowledge on the scientific and clinical background of targeted alpha therapies is summarized. Furthermore, open issues and novel approaches with a focus on the future perspective are discussed. Once these are unraveled, targeted alpha therapies with atomic in vivo nanogenerators can be tailored to suit the needs of each patient when applying careful risk stratification and combination therapies. They have the potential to become one of the major treatment pillars in modern cancer management.

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Section: Introductionmentioning

confidence: 99%

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

2020

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“… 76 Moreover, several new formulations, wherein α-generators and targeting vectors are functionalized at a high density on nanoparticle surfaces, have shown high therapeutic performances, 77 − 79 and there is increasing interest in developing targeted alpha therapy strategies for the treatment of infectious diseases. 80 For instance, several radioimmunoconjugates that targeted infected cells (rather than the viruses itself) have been developed to eliminate the virus reservoirs and prevent their propagation. 81 , 82 Recently, the first antibodies targeting SARS-CoV-2 spike proteins were discovered, providing the missing part in the development of radioimmunoconjugates that directly bind to the virus.…”

Section: Therapeutic Strategies Against Covid-19mentioning

confidence: 99%

“…Examples of promising therapeutic immunoconjugates include 225 Ac-HuM195, a lintuzumab conjugate for myeloid leukemia treatment, and 227 Th-DOTA-trastuzumab, for HER-2 positive breast and ovarian cancer treatment . Moreover, several new formulations, wherein α-generators and targeting vectors are functionalized at a high density on nanoparticle surfaces, have shown high therapeutic performances, − and there is increasing interest in developing targeted alpha therapy strategies for the treatment of infectious diseases . For instance, several radioimmunoconjugates that targeted infected cells (rather than the viruses itself) have been developed to eliminate the virus reservoirs and prevent their propagation. , Recently, the first antibodies targeting SARS-CoV-2 spike proteins were discovered, providing the missing part in the development of radioimmunoconjugates that directly bind to the virus. , Furthermore, several epitopes targeted by these antibodies are highly conserved in other coronaviruses, making such antibodies ideal candidates for targeting SARS-CoV-2 as well as other related viruses.…”

Section: Therapeutic Strategies Against Covid-19mentioning

confidence: 99%

Diagnostic, Prognostic, and Therapeutic Use of Radiopharmaceuticals in the Context of SARS-CoV-2

Pallares

Abergel

2021

ACS Pharmacol. Transl. Sci.

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The coronavirus disease 2019 (COVID-19) outbreak has devastated the healthcare systems and economies of over 200 countries in just a few months. The etiological agent of COVID-19, SARS-CoV-2, is a highly contagious virus that can be transmitted by asymptomatic and symptomatic carriers alike. While in vitro testing techniques have allowed for population-wide screening, prognostic tools are required to assess the disease severity and therapeutic response, contributing to improve the patient clinical outcomes. Moreover, no specific antiviral against COVID-19 exists at the time of publication, severely limiting treatment against the infection. Hence, there is an urgent clinical need for innovative therapeutic strategies that may contribute to manage the COVID-19 outbreak and prevent future pandemics. Herein, we critically examine recent diagnostic, prognostic, and therapeutic advancements for COVID-19 in the field of radiopharmaceuticals. First, we summarize the gold standard techniques used to diagnose COVID-19, including in vitro assays and imaging techniques, and then discuss how radionuclide-based nuclear imaging provides complementary information for prognosis and treatment management of infected patients. Second, we introduce new emerging types of radiotherapies that employ radioimmunoconjugates, which have shown selective cytotoxic response in oncological studies, and critically analyze how these compounds could be used as therapeutic agents against SARS-CoV-2. Finally, this Perspective further discusses the emerging applications of radionuclides to study the behavior of pulmonary SARS-CoV-2 aerosol particles.

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“…Given the increasing prevalence of highly resistant microorganisms, TRT has been proposed as a potential breakthrough therapeutic approach for the treatment of bacterial, viral and fungal infections [ 136 , 137 , 138 , 139 , 140 , 141 ]. In contrast to the situation in cancer treatment, where most tumor-associated targets are also expressed in normal tissues, TRT of viral infections could target virus-encoded molecules without closely related homologues in humans, promising a much higher therapeutic index.…”

Section: Use Of Radiopharmaceuticals For the Treatment Of Covid-19mentioning

confidence: 99%

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

2020

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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.

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Future Vistas in Alpha Therapy of Infectious Diseases

Cited by 8 publications

References 30 publications

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Atomic Nanogenerators in Targeted Alpha Therapies: Curie’s Legacy in Modern Cancer Management

Diagnostic, Prognostic, and Therapeutic Use of Radiopharmaceuticals in the Context of SARS-CoV-2

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

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