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Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas
Felix Neumaier1,2, Boris D Zlatopolskiy1,2, Bernd Neumaier1,2
1Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Str., 52428 Jülich, Germany.
Abstract:
Gliomas are the most common primary brain tumors in adults. A diffuse infiltrative growth pattern and high resistance to therapy make them largely incurable, but there are significant differences in the prognosis of patients with different subtypes of glioma. Mutations in isocitrate dehydrogenase (IDH) have been recognized as an important biomarker for glioma classification and a potential therapeutic target. However, current clinical methods for detecting mutated IDH (mIDH) require invasive tissue sampling and cannot be used for follow-up examinations or longitudinal studies. PET imaging could be a promising approach for non-invasive assessment of the IDH status in gliomas, owing to the availability of various mIDH-selective inhibitors as potential leads for the development of PET tracers. In the present review, we summarize the rationale for the development of mIDH-selective PET probes, describe their potential applications beyond the assessment of the IDH status and highlight potential challenges that may complicate tracer development. In addition, we compile the major chemical classes of mIDH-selective inhibitors that have been described to date and briefly consider possible strategies for radiolabeling of the most promising candidates. Where available, we also summarize previous studies with radiolabeled analogs of mIDH inhibitors and assess their suitability for PET imaging in gliomas.
Insights
Positron emission tomography (PET) imaging offers a non-invasive method to detect isocitrate dehydrogenase (IDH) mutations in gliomas. This approach could overcome limitations of invasive tissue sampling for diagnosis and monitoring.
Area of Science:
- Neuro-oncology
- Molecular Imaging
- Biomarker Discovery
Background:
- Gliomas are primary adult brain tumors with infiltrative growth and therapy resistance.
- Isocitrate dehydrogenase (IDH) mutations are key biomarkers for glioma classification and prognosis.
- Current IDH mutation detection requires invasive biopsies, limiting longitudinal studies.
Purpose of the Study:
- To review the development of PET imaging probes for non-invasively assessing IDH mutation status in gliomas.
- To explore applications of these probes beyond IDH status assessment.
- To identify challenges and strategies for developing IDH-selective PET tracers.
Main Methods:
- Review of scientific literature on IDH-selective inhibitors and PET tracer development.
- Compilation of chemical classes of IDH-selective inhibitors.
- Assessment of radiolabeled analogs for PET imaging suitability.
Main Results:
- PET imaging presents a promising non-invasive alternative to tissue biopsy for IDH mutation detection in gliomas.
- Availability of IDH-selective inhibitors provides leads for novel PET tracer development.
- Various chemical classes of inhibitors and radiolabeling strategies are discussed.
Conclusions:
- Non-invasive PET imaging of IDH mutation status in gliomas is feasible.
- Development of IDH-selective PET probes could revolutionize glioma diagnosis and management.
- Further research is needed to overcome challenges in tracer development and clinical translation.
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