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Matthew J. Oborski

Bio: Matthew J. Oborski is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Positron emission tomography & Imaging phantom. The author has an hindex of 11, co-authored 22 publications receiving 571 citations.

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TL;DR: It is expected that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment.
Abstract: Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas.

187 citations

Journal ArticleDOI
01 Mar 2019
TL;DR: In this paper, the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrastenhanced magnetic resonance imaging (DCE-MRI) data using the shutter speed model (SSM).
Abstract: This multicenter study evaluated the effect of variations in arterial input function (AIF) determination on pharmacokinetic (PK) analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data using the shutter-speed model (SSM). Data acquired from eleven prostate cancer patients were shared among nine centers. Each center used a site-specific method to measure the individual AIF from each data set and submitted the results to the managing center. These AIFs, their reference tissue-adjusted variants, and a literature population-averaged AIF, were used by the managing center to perform SSM PK analysis to estimate Ktrans (volume transfer rate constant), ve (extravascular, extracellular volume fraction), kep (efflux rate constant), and τi (mean intracellular water lifetime). All other variables, including the definition of the tumor region of interest and precontrast T1 values, were kept the same to evaluate parameter variations caused by variations in only the AIF. Considerable PK parameter variations were observed with within-subject coefficient of variation (wCV) values of 0.58, 0.27, 0.42, and 0.24 for Ktrans, ve, kep, and τi, respectively, using the unadjusted AIFs. Use of the reference tissue-adjusted AIFs reduced variations in Ktrans and ve (wCV = 0.50 and 0.10, respectively), but had smaller effects on kep and τi (wCV = 0.39 and 0.22, respectively). kep is less sensitive to AIF variation than Ktrans, suggesting it may be a more robust imaging biomarker of prostate microvasculature. With low sensitivity to AIF uncertainty, the SSM-unique τi parameter may have advantages over the conventional PK parameters in a longitudinal study.

70 citations

Journal ArticleDOI
TL;DR: Corrective actions for image scaling are suggested for manufacturers and quantitative imaging community after images generated by one of the scanners appeared to have additional intensity scaling that was not accounted for by the majority of tested quantitative image analysis SW tools.

52 citations

Journal ArticleDOI
TL;DR: The authors present the first use of the novel positron emission tomography (PET) apoptosis tracer 18F‐labeled 2‐(5‐fluoro‐pentyl)‐2‐methyl‐malonic acid (18F‐ML‐10) for early‐therapy response assessment of a newly diagnosed glioblastoma multiforme (GBM) patient.
Abstract: Objectives The authors present the first use of the novel positron emission tomography (PET) apoptosis tracer 18F-labeled 2-(5-fluoro-pentyl)-2-methyl-malonic acid (18F-ML-10) for early-therapy response assessment of a newly diagnosed glioblastoma multiforme (GBM) patient. Case report A 71-year-old male with a newly diagnosed GBM received 18F-ML-10 PET scans prior to therapy initiation (baseline) and after completing 3 weeks of whole-brain radiation therapy with concomitant temozolomide chemotherapy (early-therapy assessment, ETA). The baseline 18F-ML-10 PET scan showed increased tracer uptake at the site of the GBM, with highest activity toward the central portion of the tumor. At the ETA time point, a new distribution of tracer uptake was observed compared to baseline. Normalized pixel-by-pixel subtraction of baseline from ETA was used to quantify change in tracer distribution between 18F-ML-10 PET imaging time points. Results of this analysis showed reduction in 18F-ML-10 uptake at the site of greatest baseline uptake, but increased uptake around the periphery of the tumor at the early-therapy time point. Conclusion The changing patterns of 18F-ML-10 uptake between baseline and ETA are suggestive for therapy-induced tumor cellular apoptosis.

40 citations


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375 citations

Journal ArticleDOI
TL;DR: An overview of some of the latest methodological developments in human ultra-high field MRI/MRS as well as associated clinical and scientific applications is presented, with emphasis on techniques that particularly benefit from the changing physical characteristics at high magnetic fields.

300 citations

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TL;DR: Agarwal et al. as discussed by the authors have identified aberrant proteins in cancer cells that are attractive targets for cancer therapy, with the main difference being the nature of the toxic effects, such as vascular, dermatologic, endocrine, coagulation, immunologic, ocular and pulmonary toxicities.
Abstract: Answer questions and earn CME/CNE Advances in genomics and molecular biology have identified aberrant proteins in cancer cells that are attractive targets for cancer therapy. Because these proteins are overexpressed or dysregulated in cancer cells compared with normal cells, it was assumed that their inhibitors will be narrowly targeted and relatively nontoxic. However, this hope has not been achieved. Current targeted agents exhibit the same frequency and severity of toxicities as traditional cytotoxic agents, with the main difference being the nature of the toxic effects. Thus, the classical chemotherapy toxicities of alopecia, myelosuppression, mucositis, nausea, and vomiting have been generally replaced by vascular, dermatologic, endocrine, coagulation, immunologic, ocular, and pulmonary toxicities. These toxicities need to be recognized, prevented, and optimally managed.

285 citations

Journal ArticleDOI
TL;DR: PET gene reporter imaging can be used to monitor the trafficking of therapeutic cytotoxic T cells in glioma patients and noninvasive positron emission tomography imaging with HSV1-tk reporter gene expression present in CAR-engineered CTLs is shown to be safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients.
Abstract: High-grade gliomas are aggressive cancers that often become rapidly fatal. Immunotherapy using CD8+ cytotoxic T lymphocytes (CTLs), engineered to express both herpes simplex virus type 1 thymidine kinase (HSV1-TK) and interleukin-13 (IL-13) zetakine chimeric antigen receptor (CAR), is a treatment strategy with considerable potential. To optimize this and related immunotherapies, it would be helpful to monitor CTL viability and trafficking to glioma cells. We show that noninvasive positron emission tomography (PET) imaging with 9-[4-[18F]fluoro-3-(hydroxymethyl)butyl]guanine ([18F]FHBG) can track HSV1-tk reporter gene expression present in CAR-engineered CTLs. [18F]FHBG imaging was safe and enabled the longitudinal imaging of T cells stably transfected with a PET reporter gene in patients. Further optimization of this imaging approach for monitoring in vivo cell trafficking should greatly benefit various cell-based therapies for cancer.

251 citations

Journal ArticleDOI
TL;DR: The major molecules of PI3K signaling pathway are summarized, and the preclinical models and clinical trials of potent small-moleculePI3K inhibitors are discussed.
Abstract: Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that regulate diverse cellular processes including proliferation, adhesion, survival, and motility. Dysregulated PI3K pathway signaling occurs in one-third of human tumors. Aberrantly activated PI3K signaling also confers sensitivity and resistance to conventional therapies. PI3K has been recognized as an attractive molecular target for novel anti-cancer molecules. In the last few years, several classes of potent and selective small molecule PI3K inhibitors have been developed, and at least fifteen compounds have progressed into clinical trials as new anticancer drugs. Among these, idelalisib has advanced to phase III trials in patients with advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma. In this review, we summarized the major molecules of PI3K signaling pathway, and discussed the preclinical models and clinical trials of potent small-molecule PI3K inhibitors.

219 citations