A team of researchers from the National Cancer Institute in Gliwice, in collaboration with the Silesian Medical University in Katowice and the Institute of Cancer Research in London, has developed a novel immuno-PET imaging technique using a Zr-89-labeled antibody that could enable patients with aggressive brain tumors to benefit from breakthrough immune therapies. The results of a very promising clinical trial involving patients with newly diagnosed glioblastoma multiforme were published in the scientific journal Neuro-Oncology.
Novel imaging technique offers hope to glioblastoma multiforme patients
Published Nov. 4, 2024 09:39
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Glioblastoma multiforme is one of the most malignant brain tumors with an extremely poor prognosis. The average survival time for patients is only 12-18 months, and only 5 percent of patients survive longer than five years.
Recent studies have shown that in rapidly growing forms of glioblastoma multiforme, high expression of the PD-L1 protein found on the surface of some tumor cells and immune cells is observed. This protein acts as a "brake" on the immune system, and its blockade may allow the body to activate to fight the tumor.
PD-L1 activity can be blocked by modern immune drugs, but confirmation of the presence of this molecular target in the body is necessary before their use in a patient. To date, PD-L1 levels in brain tumors have only been assessed by biopsy, which is an invasive procedure and, in addition, provides only a snapshot of PD-L1 protein expression in the tumor and its microenvironment. Moreover, due to the high risks associated with biopsy, especially in the case of glioblastoma multiforme, these procedures are rarely performed prior to surgery, which significantly limits patients' access to modern treatments based on molecularly targeted drugs.
- To overcome these limitations, in patients with newly diagnosed glioblastoma multiforme we have used a novel radiolabel - atezolizumab labeled with the zirconium-89 isotope, which binds specifically to the PD-L1 protein. Such a radiolabel allows accurate monitoring of PD-L1 levels in real time, without the need for a biopsy, explains Prof. Gabriela Kramer-Marek, head of the Department of Radiopharmacy and PET Laboratory Imaging at the Gliwice branch of the Maria Sklodowska-Curie National Cancer Institute - National Research Institute.
A new imaging technique using a humanized Zr-89-labeled monoclonal antibody was used by researchers in a clinical trial funded by a grant from the Medical Research Agency in eight patients with newly diagnosed glioblastoma multiforme. They were injected intravenously with the radiolabeled agent, followed by immuno-PET imaging 48 and 72 hours later. The images obtained showed specific binding of the radiolabel to cells expressing PD-L1. In addition, patients who were given pembrolizumab as a neoadjuvant treatment prior to surgery showed elevated levels of the radiolabel in lymphoid tissues, which the researchers believe indicates activation of immune cells throughout the body as a response to the immunotherapy used.
- Our research demonstrates that it is possible to image an immunotherapy target using a radioimmunoassay we have developed. By being able to take a full scan of a patient's body and image the level of this target, we gain a unique opportunity to predict the body's response to therapy, monitor the immune system's response, and adjust treatment as needed. This paves the way for a personalized therapy plan based on the unique characteristics of the patient's tumor, eliminating the need for invasive biopsies prior to surgery," emphasizes Immuno-PET study leader Prof. Gabriela Kramer-Marek.
These were the first immuno-PET imaging studies using Zr-89 in Poland.
- This innovative imaging modality may represent a breakthrough in cancer therapy, allowing precise selection of patients for immunotherapy and monitoring their response to treatment in a safe and non-invasive manner," assesses Dr. Slawomir Blamek, Prof. NIO-PIB, director of the National Institute of Oncology - National Research Institute Gliwice Branch. - It is worth noting that this is not the only study conducted at NIO-PIB in Gliwice in which the use of immuno-PET imaging is planned. Preparations are underway to launch a study in which this type of imaging will be used in patients with selected advanced cancers located outside the central nervous system, adds Dr. Slawomir Blamek.
Prof. Gabriela Kramer-Marek points to even broader benefits of the new technology: - Hopefully, the use of this type of imaging will also provide us with more detailed information about the biology of the tumor itself, helping us understand why some cancers respond better to treatment than others. This will contribute to the development of more effective therapies and the optimization of existing treatments.
The results of the international clinical trial, in which the Institute of Cancer Research in London participated in addition to the National Cancer Institute in Gliwice and the Silesian Medical University, were published in late October in the journal Neuro-Oncology(https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noae190/7848401?searchresult=11). They were also reported by The Society of Nuclear Medicine and Molecular Imaging, an international scientific and professional organization that promotes the use of nuclear medicine and molecular imaging to improve patient health. The news was also widely echoed in the British media (including the Independent, Daily Mail, Daily Express, The Telegraph, The Herald, Worcester News and iNews), which called it "revolutionary" and "offering new hope" and hailed it as "a real step forward in the treatment of brain cancer."
source: press release
