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Low Dose Radiation Therapy and Convalescent Plasma: How a Hybrid Method May Maximize Benefits for COVID-19 Patients.

ABSTRACT: Physicians and scientists around the world are aggressively attempting to develop effective treatment strategies. The treatment goal is to reduce the fatality rate in 15% to 20% of individuals infected with SARS-CoV-2 who develop severe inflammatory conditions that can lead to pneumonia, and acute respiratory distress syndrome. These conditions are major causes of death in these patients. Convalescent plasma (CP) collected from patients recovered from the novel corona virus disease (COVID-19) has been considered as an effective treatment method for COVID-19. Moreover, low-dose radiation therapy (LDRT) for COVID-19 pneumonia was historically used to treat pneumonia during the first half of the 20th century. The concept of LDRT for COVID-19 pneumonia was first introduced in March 2020. Later scientists from Canada, Spain, United States, Germany and France also confirmed the potential efficacy of LDRT for treatment of COVID-19 pneumonia. The rationale behind introducing LDRT as an effective treatment method for pneumonia in COVID-19 patients is not only due to its anti-inflammatory effect, but also in optimization of the activity of the immune system. Moreover, LDRT, unlike other treatment methods such as antiviral drugs, does not have the key disadvantage of exerting a significant selective pressure on the SARS-CoV-2 virus and hence does not lead to evolution of the virus through mutations. Given these considerations, we believe that a hybrid treatment including both CP and LDRT can trigger synergistic responses that will help healthcare providers in mitigating today's COVID-19 pandemic.

SUBMITTER: H A

PROVIDER: S-EPMC7416097 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Low Dose Radiation Therapy and Convalescent Plasma: How a Hybrid Method May Maximize Benefits for COVID-19 Patients.

H Abdollahi A I Shiri S J J Bevelacqua B A Jafarzadeh J A Rahmim R H Zaidi Z S A R Mortazavi M S M J Mortazavi M

Journal of biomedical physics & engineering 20200801 4

Physicians and scientists around the world are aggressively attempting to develop effective treatment strategies. The treatment goal is to reduce the fatality rate in 15% to 20% of individuals infected with SARS-CoV-2 who develop severe inflammatory conditions that can lead to pneumonia, and acute respiratory distress syndrome. These conditions are major causes of death in these patients. Convalescent plasma (CP) collected from patients recovered from the novel corona virus disease (COVID-19) ha ...[more]

PMID: 32802787

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Project description:PurposeAlthough vascular alterations in solid tumor malignancies are known to decrease therapeutic delivery, the effects of leukemia-induced bone marrow vasculature (BMV) alterations on therapeutic delivery are not well known. Additionally, functional quantitative measurements of the leukemic BMV during chemotherapy and radiation therapy are limited, largely due to a lack of high-resolution imaging techniques available preclinically. This study develops a murine model using compartmental modeling for quantitative multiphoton microscopy (QMPM) to characterize the malignant BMV before and during treatment.Methods and materialsUsing QMPM, live time-lapsed images of dextran leakage from the local BMV to the surrounding bone marrow of mice bearing acute lymphoblastic leukemia (ALL) were taken and fit to a 2-compartment model to measure the transfer rate (Ktrans), fractional extracellular extravascular space (?ec), and vascular permeability parameters, as well as functional single-vessel characteristics. In response to leukemia-induced BMV alterations, the effects of 2 to 4 Gy low-dose radiation therapy (LDRT) on the BMV, drug delivery, and mouse survival were assessed post-treatment to determine whether neoadjuvant LDRT before chemotherapy improves treatment outcome.ResultsMice bearing ALL had significantly altered Ktrans, increased ?ec, and increased permeability compared with healthy mice. Angiogenesis, decreased single-vessel perfusion, and decreased vessel diameter were observed. BMV alterations resulted in disease-dependent reductions in cellular uptake of Hoechst dye. LDRT to mice bearing ALL dilated BMV, increased single-vessel perfusion, and increased daunorubicin uptake by ALL cells. Consequently, LDRT administered to mice before receiving nilotinib significantly increased survival compared with mice receiving LDRT after nilotinib, demonstrating the importance of LDRT conditioning before therapeutic administration.ConclusionThe developed QMPM enables single-platform assessments of the pharmacokinetics of fluorescent agents and characterization of the BMV. Initial results suggest BMV alterations after neoadjuvant LDRT may contribute to enhanced drug delivery and increased treatment efficacy for ALL. The developed QMPM enables observations of the BMV for use in ALL treatment optimization.

Dataset Information

Low Dose Radiation Therapy and Convalescent Plasma: How a Hybrid Method May Maximize Benefits for COVID-19 Patients.

Publications

Low Dose Radiation Therapy and Convalescent Plasma: How a Hybrid Method May Maximize Benefits for COVID-19 Patients.

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