Reston, VA-Nuclear medicine has the potential to change the landscape of theranostics in neurooncology, according to a new article published in the February issue of The Journal of Nuclear Medicine (JNM). With recent advances in techniques to permeate the brain-blood barrier (BBB), the prospect of using radiopharmaceuticals to treat brain tumors, such as meningiomas, gliomas, brain metastases, and pediatric brain tumors, is promising.
"In the last decade, we have observed a huge step forward in treatment options for a wide range of tumors in terms of both survival and quality of life. However, therapeutic approaches to brain tumors remain a challenge, with considerable limitations regarding delivery of drugs," stated the article's authors. "There has been renewed and increasing interest in translating the popular theranostic approach well known from prostate and neuroendocrine cancer to neurooncology. Although far from perfect, some of these approaches show encouraging preliminary results."
In this state-of-the-art JNM article, authors provided a general overview of the use of theranostics for four areas of neurooncology and provided perspectives on future research needs. The article focused on meningiomas, gliomas, brain metastases, and pediatric brain tumors.
Meningiomas are the brain tumors for which peptide receptor radionuclide therapy (PRRT) has been most performed. It is currently used in meningiomas that cannot be treated with surgery or conventional radiation therapy regardless of their grade. Most of the available data on PRRT in meningiomas are from patients at a late stage of the disease when the efficacy of the treatment is potentially limited. It might be advantageous, state the authors, to start PRRT earlier in the disease course before patients develop treatment-refractory, progressive, and extensive disease. Future studies should include the development of criteria for appropriate use of PRRT in specific subtypes and the determination of efficacy in randomized prospective trials, as well as focus on treatment combinations.
Gliomas are the most common malignant brain tumors, with around 80 percent of tumors considered high-grade. Many potential theranostic targets for gliomas have been investigated, with variable but mostly discouraging results. Future studies should focus on patient selection and using multimodal approaches combining theranostic agents with techniques enhancing BBB or blood-tumor barrier (BTB) permeability.
Current therapeutic options for brain metastases consist of a combination of surgery, external radiation therapy, and targeted and immune-modulating therapies. As primary cancer control is advancing dramatically, brain metastases across many cancer types occur more frequently, and more effective therapies are needed. Radionuclide therapy for brain metastases has been scarcely investigated; however, an advantage of radionuclide therapy over immune therapy is that the effective targeting of all lesions can be visualized using intratherapy scanning. Moreover, the effective targeting of brain metastases can be monitored by PET imaging. These features might translate into an advantage over the current standard of care in terms of clinical benefit.
Pediatric brain tumors are the most frequent solid malignancy in childhood and account for 20 percent of all pediatric tumors. Surgery is the mainstay in many pediatric brain tumors and can be combined with external radiation therapy or chemotherapy, although this is not ideal for young patients. A relatively large quantity of literature is available on theranostic approaches to the use of radioligands in pediatric neurooncology; the best-documented and most-promising approach is the use of intracranioventricular 131I-omburtamab for treatment of leptomeningeal disease.
The main obstacle in neurooncology compared with other solid tumors is getting therapeutics through the BBB and the BTB. Several strategies have been developed to bypass them, and these potential pathways can allow therapeutics to be directly administered to the tumor or into surgical or anatomical cavities.
"The success of most theranostic agents will depend on the development and clinical implementation of principles that increase the permeability of the BBB," state the authors. "Here, nuclear medicine techniques can aid and potentially speed development by enabling visualization and verification of the principle."
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| Figure 1. Example of interventional approaches to bypass physiologic blood-brain barrier (BBB) and blood-tumor barrier (BTB). Normal transport in BBB is not included. (Left) Local delivery with administration of radioactivity directly into resection cavity. (Middle) CED: microcatheter is implanted into tumor, and hydraulic pressure is used to distribute drugs in brain parenchyma. (Right) FUS reshapes BBB using targeted ultrasonic wave. This in turn causes interaction between administered microbubbles and capillary bed, resulting in enhanced vessel permeability. |
The authors of "Theranostics in Neurooncology: Heading Toward New Horizons" include Nelleke Tolboom, Department of Radiology and Nuclear Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands; Antoine Verger, IADI, INSERM, UMR 1254, Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU-Nancy, Université de Lorraine, Nancy, France; Nathalie L. Albert, Department of Nuclear Medicine, University Hospital of Munich, Munich, Germany; Francesco Fraioli, Institute of Nuclear Medicine, University College London, London, United Kingdom; Eric Guedj, Département de Médecine Nucléaire, Hôpital de la Timone, CERIMED, Institut Fresnel, Aix Marseille University, APHM, CNRS, Centrale Marseille, Marseille, France; Tatjana Tarub-Weidinger, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria; Silvia Morbelli, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, and Nuclear Medicine Unit, Department of Health Sciences, University of Genoa, Genoa, Italy; Ken Herrmann, Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium-University Hospital Essen, Essen, Germany; Pietro Zucchetta, Department of Nuclear Medicine, University Hospital of Padova, Padova, Italy; Sabine L.A. Plasschaert, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands; Igo Yakushev, Department of Nuclear Medicine, School of Medicine, Technical University of Munich and Munich Center for Neurosciences-Brain and Mind, Munich, Germany; Michael Weller, Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland; Martin Glas, Division of Clinical Neurooncology, Department of Neurology and Center for Translational Neuro- and Behavioral Sciences, University Medicine Essen, University Duisburg-Essen and German Cancer Consortium, Essen, Germany; Matthias Preusser, Division of Oncology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; Diego Cecchin, Nuclear Medicine Unit, Department of Medicine-DIMED, University Hospital of Padua, Padua, Italy; Henryk Barthel, Department of Nuclear Medicine, Leipzig University Medical Centre, Leipzig, Germany; and Donatienne Van Weehaeghe, Department of Radiology and Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.
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