Day: 03/11/2022
Two months after historic transplant, first person to receive gene-edited pig heart dies.
Two months after historic transplant, first person to receive gene-edited pig heart dies, World News | wionews.com https://www.wionews.com/world/two-months-after-historic-transplant-first-person-to-receive-gene-edited-pig-heart-dies-460677
Xenotransplantation – Will animal-to-human organ transplant succeed in the near future?
PET Imaging for Oropharynx Cancer Could De-escalate Therapy, Reducing Side Effects
PET scans obtained before and midway through treatment for p16-positive oropharynx cancer (OPC) can help determine whether a patient can receive a lower dose of radiation therapy in the second half of their treatment course without compromising cancer control. A new phase II trial reports that patients in the trial who received de-escalated therapy experienced fewer short-term side effects than those who received standard therapy.
The study presented at the 2022 Multidisciplinary Head and Neck Cancers Symposium focused on imaging using fluorodeoxyglucose (FDG) to detect responses to chemoradiation for p16+ oropharynx cancer. While FDG is the most commonly used radiotracer in clinical PET imaging, this trial is the first to report its use as a mid-treatment imaging marker to guide de-escalation for OPC.
Patients in this multi-institution trial had FDG-PET scans to determine their metabolic tumor volume before and midway through treatment. The current analysis reports findings for the first 59 patients accrued to the trial. Those who had tumors with lower metabolic activity before treatment and more than 50% reduction in metabolic tumor volume after two weeks of treatment were de-escalated – specifically, treatment stopped at a total dose of 54 Gy in 27 fractions, rather than the standard total dose of 70 Gy in 35 fractions. All patients received concurrent weekly carboplatin/paclitaxel chemotherapy.
“Advanced imaging helps physicians personalize therapy based on patients’ individual tumor characteristics and response to treatment. By incorporating FDG-PET scans before and midway through treatment, we were able to adjust the radiation dose for about half of our patients and reduce their short-term side effects while still focusing on tumor control,” said lead author Steven Allen, MD, PhD, a radiation oncology resident at the University of Michigan.
Half of the patients met de-escalation criteria and received the lower radiation dose, resulting in approximately 25% less radiation exposure to the sensitive structures in the head and neck known to be associated with side effects during treatment. Patients in the de-escalated group had significantly less weight loss during treatment (6% vs. 11% from baseline, p<0.001), were less likely to need a feeding tube (1 vs. 7 patients, p=0.037) and had improved swallowing function on a video swallow study administered after treatment (p=0.036).
“We anticipated long-term improvements in side effects, but the short-term improvements were better than expected,” said senior author and principal investigator Michelle L Mierzwa, MD, Associate Chair of Clinical Research and Co-Chair of Head and Neck Clinical Trials at the University of Michigan. “Experiencing fewer short-term side effects potentially allows patients to get back to their normal activities more quickly.”
Radiotracer Enables Real-time Imaging of Innate Immune Activity
A new radio-labeled molecule capable of selectively reacting with certain high-energy radicals that are characteristic of innate immune activity may allow a non-invasive approach to monitor inflammation in real time by positron emission tomography (PET) imaging. Researchers at The University of Texas MD Anderson Cancer Center utilized new chemistry techniques to synthesize 4-[18F]Fluoro-1-Naphthol ([18F]4FN) as a novel reporter of myeloperoxidase (MPO) activity – a key enzyme active in the innate immune response. The molecule may be able to pinpoint areas of inflammation in a variety of clinical settings, such as inflammatory diseases, infections and immunotherapy-related side effects. The preclinical study was published in Nature Biotechnology.
“There has been a long-standing interest in imaging inflammation and redox in general, but most current approaches generate high levels of background noise from biological processes that generate lower-energy radicals,” said corresponding author David Piwnica-Worms, MD, PhD, chair of Cancer Systems Imaging. “Our molecule is tuned toward inflammation mediated by high-energy radicals, offering the potential to selectively monitor activation of innate immunity.”
The innate immune response is the body’s first line of defense against invading pathogens. In contrast to the adaptive immune response, innate immunity is nonspecific and acts broadly against infections or foreign agents. Innate immunity is largely driven by myeloid cells, including neutrophils, macrophages and natural killer (NK) cells.
Myeloperoxidase is a highly conserved feature of the innate immune response across myeloid cells. This proinflammatory enzyme is activated by hydrogen peroxide to produce a variety of high-energy radicals that are used to eliminate pathogens.
Co-led by Federica Pisaneschi, PhD, assistant professor, and Seth T. Gammon, PhD, associate professor of Cancer Systems Imaging, the research team focused on MPO activity to develop a redox-tuned reporter specific to innate immune activity. Using newly developed chemistry techniques, the team was able to synthesize [18F]4FN as a labeled molecule to selectively bind nearby proteins and cells when [18F]4FN has been oxidized by MPO plus hydrogen peroxide, but not hydrogen peroxide alone.
The researchers evaluated the potential uses of [18F]4FN as an in vivo PET imaging tool in several laboratory models of inflammation. The molecule was able to successfully highlight inflammation from acute toxic shock, arthritis and contact dermatitis, ailments known to be mediated by activation of innate immunity. In addition, their results suggest [18F]4FN is a more specific and robust reporter of inflammation than other clinically utilized PET imaging agents, such as fluorodeoxyglucose ([18F]FDG).
“We need to verify this PET imaging agent in clinical studies, but it certainly has the potential for broad applications that could benefit patients across all kinds of diseases and clinical scenarios,” Dr. Piwnica-Worms said. “A tool like this could be used to identify multi-focal hotspots of inflammation, allowing physicians to intervene before disease progression or to follow the resolution of symptoms during therapy.”
The research team is in discussions with clinical collaborators to test specific applications of [18F]4FN. An initial study, now under Food and Drug Administration review for Investigational New Drug registration and Institutional Review Board approval, will evaluate [18F]4FN as an early biomarker of immune-related adverse events in patients being treated with immune checkpoint inhibitors.
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