Browsing by Author "Sanders, Keith"

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    MR-Guided Adaptive Radiotherapy for OAR Sparing in Head and Neck Cancers
    (MDPI, 2022) Mulder, Samuel L.; Heukelom, Jolien; McDonald, Brigid A.; Van Dijk, Lisanne; Wahid, Kareem A.; Sanders, Keith; Salzillo, Travis C.; Hemmati, Mehdi; Schaefer, Andrew; Fuller, Clifton D.
    MR-linac devices offer the potential for advancements in radiotherapy (RT) treatment of head and neck cancer (HNC) by using daily MR imaging performed at the time and setup of treatment delivery. This article aims to present a review of current adaptive RT (ART) methods on MR-Linac devices directed towards the sparing of organs at risk (OAR) and a view of future adaptive techniques seeking to improve the therapeutic ratio. This ratio expresses the relationship between the probability of tumor control and the probability of normal tissue damage and is thus an important conceptual metric of success in the sparing of OARs. Increasing spatial conformity of dose distributions to target volume and OARs is an initial step in achieving therapeutic improvements, followed by the use of imaging and clinical biomarkers to inform the clinical decision-making process in an ART paradigm. Pre-clinical and clinical findings support the incorporation of biomarkers into ART protocols and investment into further research to explore imaging biomarkers by taking advantage of the daily MR imaging workflow. A coherent understanding of this road map for RT in HNC is critical for directing future research efforts related to sparing OARs using image-guided radiotherapy (IGRT).
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    Pancreatic tumor microenvironmental acidosis and hypoxia transform gold nanorods into cell-penetrant particles for potent radiosensitization
    (AAAS, 2022) Rauta, Pradipta Ranjan; Mackeyev, Yuri; Sanders, Keith; Kim, Joseph B.K.; Gonzalez, Valeria V.; Zahra, Yasmin; Shohayeb, Muhammad A.; Abousaida, Belal; Vijay, Geraldine V.; Tezcan, Okan; Derry, Paul; Liopo, Anton V.; Zubarev, Eugene R.; Carter, Rickey; Singh, Pankaj; Krishnan, Sunil
    Coating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate in the periphery and core of tumors without any signs of serum biochemical or hematological alterations, normal organ histopathological abnormalities, or overt deterioration in animal health. Furthermore, P(Glu-co-Lys)-GNRs penetrated the tumor microenvironment to accumulate in the hypoxic cores of tumors to potently radiosensitize heterotopic and orthotopic pancreatic cancers in vivo.