Michael S. Petronek

Michael S. Petronek
University of Iowa | UI · Department of Radiation Oncology

Doctor of Philosophy

About

64
Publications
4,122
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
627
Citations
Introduction
Education
August 2017 - December 2022
University of Iowa
Field of study
  • Free Radical and Radiation Biology
August 2015 - May 2017
Cleveland State University
Field of study
  • Medical Physics
August 2011 - May 2015
Allegheny College
Field of study
  • Physics

Publications

Publications (64)
Article
For decades the field of radiation oncology has sought to improve the therapeutic ratio through innovations in physics, chemistry, and biology. To date, technological advancements in image guided beam delivery techniques have provided clinicians with their best options for improving this critical tool in cancer care. Medical physics has focused on...
Article
Full-text available
Iron (Fe) is an essential element that plays a fundamental role in a wide range of cellular functions, including cellular proliferation, DNA synthesis, as well as DNA damage and repair. Because of these connections, iron has been strongly implicated in cancer development. Cancer cells frequently have changes in the expression of iron regulatory pro...
Article
Full-text available
Pharmacological ascorbate (P-AscH⁻) combined with standard of care (SOC) radiation and temozolomide is being evaluated in a phase 2 clinical trial (NCT02344355) in the treatment of glioblastoma (GBM). Previously published data demonstrated that paramagnetic iron (Fe³⁺) catalyzes ascorbate's oxidation to form diamagnetic iron (Fe²⁺). Because paramag...
Article
Enriched iron metabolic features such as high transferrin receptor (TfR) expression and high iron content are commonly observed in aggressive gliomas and can be associated with poor clinical responses. However, the underlying question of how iron contributes to tumor aggression remains elusive. Gliomas harboring isocitrate dehydrogenase (IDH) mutat...
Article
Full-text available
Glioblastoma (GBM) is the most common primary brain malignancy in the U.S. with a 5-year overall survival < 5% despite an aggressive standard of care. Laser interstitial thermal therapy (LITT) is a surgical approach to treating GBM that has gained traction, providing a safe option for reducing intracranial tumor burden. LITT is believed to potentia...
Article
Full-text available
Gallium-based therapy has been considered a potentially effective cancer therapy for decades and has recently re-emerged as a novel therapeutic strategy for the management of glioblastoma tumors. Gallium targets the iron-dependent phenotype associated with aggressive tumors by mimicking iron in circulation and gaining intracellular access through t...
Article
Full-text available
Nanotechnology has provided considerable advancements in an array of disciplines. Recently, it has been shown that ferumoxytol, a magnetite (Fe3O4) nanoparticle, can be oxidized by ionizing radiation. Ferumoxytol nanoparticles have high stability, and thus can be hypothesized that they have dosimetric potential. In this study, it has been observed...
Article
Full-text available
Conventional cancer therapy strategies, although centered around killing tumor cells, often lead to severe side effects on surrounding normal tissues, thus compromising the chronic quality of life in cancer survivors. Hydrogen peroxide (H2O2) is a secondary signaling molecule that has an array of functions in both tumor and normal cells, including...
Article
Full-text available
The MR transverse relaxation rate, R2*, has been widely used to detect iron and myelin content in tissue. However, it is also sensitive to macroscopic B0 inhomogeneities. One approach to correct for the B0 effect is to fit gradient-echo signals with the three-parameter model, a sinc function-weighted monoexponential decay. However, such three-param...
Article
Full-text available
Soft tissue sarcomas (STSs) are mesenchymal malignant lesions that develop in soft tissues. Despite current treatments, including radiation therapy (RT) and surgery, STSs can be associated with poor patient outcomes and metastatic recurrences. Neoadjuvant radiation therapy (nRT), while effective, is often accompanied by severe postoperative wound h...
Article
High dose Vitamin C (pharmacological ascorbate; P-AscH‒ > 20 mM plasma levels) given intravenously (I.V.), has made a remarkable re-emergence as an adjuvant to combined modality approaches in cancer therapy. P-AscH‒ can be readily oxidized in the presence of redox active metals (i.e., P-AscH‒ serves as an iron reducing agent), which can result in i...
Article
Full-text available
Cancer cells frequently present elevated intracellular iron levels, which are thought to facilitate an enhanced proliferative capacity. Targeting iron metabolism within cancer cells presents an avenue to enhance therapeutic responses, necessitating the use of non-invasive models to modulate iron manipulation to predict responses. Moreover, the ubiq...
Article
Full-text available
Background: Radiation therapy (RT) is an integral and commonly used therapeutic modality for primary lung cancer. However, radiation-induced lung injury (RILI) limits the irradiation dose used in the lung and is a significant source of morbidity. Disruptions in iron metabolism have been linked to radiation injury, but the underlying mechanisms rema...
Article
Full-text available
Background Pharmacological ascorbate (intravenous delivery reaching plasma concentrations ≈ 20 mM; P-AscH⁻) has emerged as a promising therapeutic strategy for glioblastoma. Recently, a single-arm phase 2 clinical trial demonstrated a significant increase in overall survival when P-AscH⁻ was combined with temozolomide and radiotherapy. As P-AscH⁻ r...
Article
Full-text available
Recently, the FDA-approved iron oxide nanoparticle, ferumoxytol, has been found to enhance the efficacy of pharmacological ascorbate (AscH −) in treating glioblastoma, as AscH − reduces the Fe 3+ sites in the nanoparticle core. Given the iron oxidation state specificity of T2* relaxation mapping, this study aims to investigate the ability of T2* re...
Article
Full-text available
Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to bett...
Article
Full-text available
The intracellular redox-active labile iron pool (LIP) is weakly chelated and available for integration into the iron metalloproteins that are involved in diverse cellular processes, including cancer cell-specific metabolic oxidative stress. Abnormal iron metabolism and elevated LIP levels are linked to the poor survival of lung cancer patients, yet...
Article
Purpose Pharmacologic ascorbate (P-AscH−) is hypothesized to be an iron (Fe)-dependent tumor-specific adjuvant to chemoradiation in treating glioblastoma (GBM). This study determined the efficacy of combining P-AscH− with radiation and temozolomide in a phase II clinical trial while simultaneously investigating a mechanism-based, noninvasive biomar...
Article
BACKGROUND AND OBJECTIVES Meningeal solitary fibrous tumors (SFTs) comprise 0.4% of primary central nervous system neoplasms and carry metastatic potential. Disease course and optimal management are largely unknown, and there is currently no literature rigorously describing neurological outcomes in surgically managed SFTs. We present one of the lar...
Article
Full-text available
A distinctive feature of cancer is the upregulation of sirtuin proteins. Sirtuins are class III NAD+-dependent deacetylases involved in cellular processes such as proliferation and protection against oxidative stress. SIRTs 1 and 2 are also overexpressed in several types of cancers including non-small cell lung cancer (NSCLC). Sirtinol, a sirtuin (...
Article
Full-text available
Iron accumulation and ferroptosis have long been implicated in the pathogenesis and neuronal loss of parkinson’s disease. With the growing discovery of genes associated with parkinson’s disease and mitochondrial function, there’s emerging evidence of the convergent role of mitochondrial dysfunction, subsequent reactive oxygen species (ROS) generati...
Article
Full-text available
Iron-sulfur (Fe-S) clusters are unique, redox-active co-factors ubiquitous throughout cellular metabolism. Fe-S cluster synthesis, trafficking, and coordination result from highly coordinated, evolutionarily conserved biosynthetic processes. The initial Fe-S cluster synthesis occurs within the mitochondria; however, the maturation of Fe-S clusters...
Article
Full-text available
Ferumoxytol (FMX) is an FDA-approved magnetite (Fe3O4) nanoparticle used to treat iron deficiency anemia that can also be used as an MR imaging agent in patients that can't receive gadolinium. Pharmacological ascorbate (P-AscH-; IV delivery; plasma levels ≈ 20 mM) has shown promise as an adjuvant to standard of care chemo-radiotherapy in glioblasto...
Article
Full-text available
Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HN...
Article
Background Ultra-high dose-rate radiotherapy (FLASH-RT) affords improvements in the therapeutic index by minimizing normal tissue toxicities without compromising anti-tumor efficacy compared to conventional dose rate radiotherapy (CONV-RT). To investigate the translational potential of FLASH-RT to human pediatric medulloblastoma brain tumor, we use...
Article
Purpose: Ataxia telangiectasia mutated kinase (ATM) inhibitors are potent radiosensitizers that regulate DNA damage responses and redox metabolism, but they have not been translated clinically because of the potential for excess normal tissue toxicity. Pharmacologic Ascorbate (P-AscH-; IV administration achieving mM plasma concentrations) selectiv...
Article
Full-text available
Pharmacological ascorbate (i.e., intravenous infusions of vitamin C reaching ~ 20 mM in plasma) is under active investigation as an adjuvant to standard of care anti-cancer treatments due to its dual redox roles as an antioxidant in normal tissues and as a prooxidant in malignant tissues. Immune checkpoint inhibitors (ICIs) are highly promising the...
Article
Full-text available
Polyoxometalate nanoparticles (POMs) are a class of compounds made up of multiple transition metals linked together using oxygen atoms. POMs commonly include group 6 transition metals, with two of the most common forms using molybdenum and tungsten. POMs are suggested to exhibit antimicrobial effects. In this study, we developed two POM preparation...
Article
Purpose/Objective(s): The ATM protein is key to DNA double strand break (DSB) repair and ATM inhibitors are potent radiosensitizers. Clinical translation of these agents in combination with radiotherapy (RT) has been limited due to concerns for increased normal tissue toxicity. Pharmacologic Ascorbate (P-AscH-) radiosensitizes cancer cells via gene...
Article
Background: Cancer cells often have altered iron metabolism relative to non-malignant cells with increased transferrin receptor and ferritin expression. Targeting iron regulatory proteins as part of a cancer therapy regimen is currently being investigated in various malignancies. Anti-cancer therapies that exploit the differences in iron metabolis...
Article
Full-text available
Purpose Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical tr...
Article
Full-text available
Ferumoxytol (FMX) is an iron oxide nanoparticle that is FDA approved for the treatment of iron deficiency anemia. FMX contains an Fe3O4 core. Currently, the redox chemistry of Fe3O4 nanoparticles remains relatively unexplored. FMX has recently gained interest as an anti-cancer agent. Ionizing radiation (IR) is a treatment modality employed to treat...
Article
Purpose/Objective(s) Ataxia telangiectasia mutated protein (ATM) is one of the key sensors of DNA damage and specific inhibitors of ATM are potent radiosensitizers. However, their clinical utility with radiation (RT) is limited because they lack tissue specificity and increase normal tissue injury. Pharmacologic (high dose) ascorbate (P-AscH⁻) sele...
Article
Full-text available
T 2 * relaxation is an intrinsic magnetic resonance imaging (MRI) parameter that is sensitive to local magnetic field inhomogeneities created by the deposition of endogenous paramagnetic material (e.g. iron). Recent studies suggest that T 2 * mapping is sensitive to iron oxidation state. In this study, we evaluate the spin state-dependence of T 2 *...
Article
Full-text available
Interest in the use of pharmacological ascorbate as a treatment for cancer has increased considerably since it was introduced by Cameron and Pauling in the 1970s. Recently, pharmacological ascorbate has been used in preclinical and early-phase clinical trials as a selective radiation sensitizer in cancer. The results of these studies are promising....
Article
Full-text available
Cancer cells preferentially accumulate iron (Fe) relative to non-malignant cells; however, the underlying rationale remains elusive. Iron–sulfur (Fe–S) clusters are critical cofactors that aid in a wide variety of cellular functions (e.g., DNA metabolism and electron transport). In this article, we theorize that a differential need for Fe–S biogene...
Conference Paper
PURPOSE: First line treatment with platinum-based chemotherapy with or without immunotherapy improves survival in metastatic non-small cell lung cancer (NSCLC). Preclinical studies suggest that pharmacological ascorbate (P-AscH-) enhances tumor response to platinum therapy. Hence, we conducted a single-arm phase II study to evaluate the efficacy of...
Article
3609 Background: Ataxia telangectasia mutated protein (ATM) is one of the key sensors of DNA damage and specific inhibitors of ATM are potent radiosensitizers. However, their clinical utility with radiation (RT) is limited because they lack tissue specificity and increase normal tissue injury. Pharmacologic (high dose) ascorbate (P-AscH ⁻ ) selecti...
Article
Full-text available
Pharmacological ascorbate (P-AscH-; high dose intravenous infusions of vitamin C generating milli-molar plasma concentrations) has re-emerged as an anti-cancer therapy. Phase 1 clinical trials combining P-AscH- with chemotherapy and ionizing radiation demonstrate safety and promising clinical outcomes in a variety of malignancies. In a first-in-hum...
Article
Full-text available
There is a rapidly growing body of literature supporting the notion that differential oxidative metabolism in cancer versus normal cells represents a metabolic frailty that can be exploited to open a therapeutic window into cancer therapy. These cancer cell-specific metabolic frailties may be amenable to manipulation with non-toxic small molecule r...
Article
Full-text available
MR-linac technology enhances the precision of therapeutic radiation by clarifying the tumor-normal tissue interface and provides the potential for adaptive treatment planning. Accurate delineation of tumors on diagnostic magnetic resonance imaging (MRI) frequently requires gadolinium-based contrast agents (GBCAs). Despite generally being considered...
Article
Full-text available
Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patient...
Chapter
Metabolic reprogramming is a hallmark of cancer. Altered metabolism provides a survival advantage for cancer cells during tumorigenesis by supplying resources needed for uncontrolled growth and increased rates of cell division. As tumors grow beyond the limits of diffusion, altered metabolism provides a selective advantage in the context of nutrien...
Article
Full-text available
Patients diagnosed with metastatic sarcoma have limited options for achieving both local and distant tumor control. While SBRT can achieve local control, distant response rates remain low. There is limited evidence demonstrating the safety and efficacy for combining SBRT with concurrent PD-1 checkpoint blockade in metastatic sarcoma. In this prospe...
Article
2552 Background: Identification of tumor characteristics that may be associated with survival in patients with glioblastoma (GBM) has been largely characterized by IDH mutations and MGMT promoter methylation status. However, these genetic changes and other currently available data are not sufficient to explain the longevity experienced by a subset...
Article
Purpose: The majority of colorectal cancers are resistant to cancer immune-checkpoint inhibitors. Ionizing radiation (IR) and several radiosensitizers, including PARP inhibitors, can enhance responsiveness to immune checkpoint inhibitors by potentially complementary mechanisms of action. We assessed the ability of radiation and PARP-inhibition to...
Article
Full-text available
Purpose: The greater soft tissue contrast of magnetic resonance imaging (MRI) allows improved accuracy in prostate contouring compared to transrectal ultrasound (TRUS) and helps in identifying specific regions within the prostate. This study attempts to evaluate the potential benefit of MRI-TRUS fusion in treatment planning for more accurate prost...
Conference Paper
Introduction: Many human cancers, including microsatellite stable (MSS) colorectal cancers (CRC), are resistant to immunotherapies including T-cell checkpoint inhibitors (CPIs). Stereotactic body radiotherapy (SBRT) has shown some promise in improving systemic immune responses to CPIs in preclinical studies although results from clinical trials hav...
Conference Paper
Introduction: Many human cancers, including microsatellite stable (MSS) colorectal cancers (CRC), are resistant to immunotherapies including T-cell checkpoint inhibitors (CPIs). Stereotactic body radiotherapy (SBRT) has shown some promise in improving systemic immune responses to CPIs in preclinical studies although results from clinical trials hav...
Article
Based on encouraging results from several early-phase clinical trials, there is renewed interest in the use of pharmacological ascorbate (i.e., intravenous administration resulting in >≈10 mM plasma ascorbate concentrations) in combination with standard-of-care cancer treatments including radiation and/or chemotherapy. Under normal, healthy physiol...
Article
Purpose:Transrectal Ultrasound (TRUS) imaging is utilized intra-operatively for LDR permanent prostate seed implant treatment planning. Prostate contouring with TRUS can be challenging at the apex and base. This study attempts to improve accuracy of prostate contouring with MRI-TRUS fusion to prevent over- or under-estimation of the prostate volume...

Network

Cited By