Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

Neumaier, Felix; Zlatopolskiy, Boris D.; Neumaier, Bernd

doi:10.3390/molecules28072890

Cited by 7 publications

(1 citation statement)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IDH mutations, particularly in IDH1 and IDH2 genes, are mutually exclusive and have significant implications for tumor behavior and patient prognosis [ 7 ]. Gliomas with IDH mutations are associated with better overall survival and response to treatment compared to IDH wild-type gliomas [ 8 ]. Therefore, the assessment of IDH mutation status is crucial for accurate glioma classification and treatment planning.…”

Section: Introductionmentioning

confidence: 99%

Beyond invasive biopsies: using VASARI MRI features to predict grade and molecular parameters in gliomas

Setyawan,

Choridah,

Nugroho

et al. 2024

Cancer Imaging

View full text Add to dashboard Cite

Background Gliomas present a significant economic burden and patient management challenge. The 2021 WHO classification incorporates molecular parameters, which guide treatment decisions. However, acquiring these molecular data involves invasive biopsies, prompting a need for non-invasive diagnostic methods. This study aims to assess the potential of Visually AcceSAble Rembrandt Images (VASARI) MRI features to predict glioma characteristics such as grade, IDH mutation, and MGMT methylation status. Methods This study enrolled 107 glioma patients treated between 2017 and 2022, meeting specific criteria including the absence of prior chemotherapy/radiation therapy, and the presence of molecular and MRI data. Images were assessed using the 27 VASARI MRI features by two blinded radiologists. Pathological and molecular assessments were conducted according to WHO 2021 CNS Tumor classification. Cross-validation Least Absolute Shrinkage and Selection Operator (CV-LASSO) logistic regression was applied for statistical analysis to identify significant VASARI features in determining glioma grade, IDH mutation, and MGMT methylation status. Results The study demonstrated substantial observer agreement in VASARI feature evaluation (inter- and intra-observer κ = 0.714 - 0.831 and 0.910, respectively). Patient imaging characteristics varied significantly with glioma grade, IDH mutation, and MGMT methylation. A predictive model was established using VASARI features for glioma grade prediction, exhibiting an AUC of 0.995 (95% CI = 0.986 – 0.998), 100% sensitivity, and 92.86% specificity. IDH mutation status was predicted with AUC 0.930 (95% CI = 0.882 - 0.977), and improved slightly to 0.933 with 'age-at-diagnosis' added. A model predicting MGMT methylation had a satisfactory performance (AUC 0.757, 95% CI = 0.645 - 0.868), improving to 0.791 when 'age-at-diagnosis' was added. Conclusions The T1/FLAIR ratio, enhancement quality, hemorrhage, and proportion enhancing predict glioma grade with excellent accuracy. The proportion enhancing, thickness of enhancing margin, and T1/FLAIR ratio are significant predictors for IDH mutation status. Lastly, MGMT methylation is related to the longest diameter of the lesion, edema crossing the midline, and the proportion of the non-enhancing lesion. VASARI MRI features offer non-invasive and accurate predictive models for glioma grade, IDH mutation, and MGMT methylation status, enhancing glioma patient management.

show abstract

Section: Introductionmentioning

confidence: 99%

Beyond invasive biopsies: using VASARI MRI features to predict grade and molecular parameters in gliomas

Setyawan,

Choridah,

Nugroho

et al. 2024

Cancer Imaging

View full text Add to dashboard Cite

show abstract

Radiosynthesis and biological evaluation of [18F]AG-120 for PET imaging of the mutant isocitrate dehydrogenase 1 in glioma

Lai,

Wenzel,

Dukić-Stefanović

et al. 2023

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Glioma are clinically challenging tumors due to their location and invasiveness nature, which often hinder complete surgical resection. The evaluation of the isocitrate dehydrogenase mutation status has become crucial for effective patient stratification. Through a transdisciplinary approach, we have developed an 18F-labeled ligand for non-invasive assessment of the IDH1R132H variant by using positron emission tomography (PET) imaging. In this study, we have successfully prepared diastereomerically pure [18F]AG-120 by copper-mediated radiofluorination of the stannyl precursor 6 on a TRACERlab FX2 N radiosynthesis module. In vitro internalization studies demonstrated significantly higher uptake of [18F]AG-120 in U251 human high-grade glioma cells with stable overexpression of mutant IDH1 (IDH1R132H) compared to their wild-type IDH1 counterpart (0.4 vs. 0.013% applied dose/µg protein at 120 min). In vivo studies conducted in mice, exhibited the excellent metabolic stability of [18F]AG-120, with parent fractions of 85% and 91% in plasma and brain at 30 min p.i., respectively. Dynamic PET studies with [18F]AG-120 in naïve mice and orthotopic glioma rat model reveal limited blood-brain barrier permeation along with a low uptake in the brain tumor. Interestingly, there was no significant difference in uptake between mutant IDH1R132H and wild-type IDH1 tumors (tumor-to-blood ratio[40−60 min]: ~1.7 vs. ~1.3). In conclusion, our preclinical evaluation demonstrated a target-specific internalization of [18F]AG-120 in vitro, a high metabolic stability in vivo in mice, and a slightly higher accumulation of activity in IDH1R132H-glioma compared to IDH1-glioma. Overall, our findings contribute to advancing the field of molecular imaging and encourage the evaluation of [18F]AG-120 to improve diagnosis and management of glioma and other IDH1R132H-related tumors.

show abstract

Molecular imaging of IDH-mutant gliomas in the new era of IDH inhibitors: preparing for future challenges

Ninatti,

Moresco,

Sollini

2024

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Mutated Isocitrate Dehydrogenase (mIDH) as Target for PET Imaging in Gliomas

Cited by 7 publications

References 115 publications

Beyond invasive biopsies: using VASARI MRI features to predict grade and molecular parameters in gliomas

Beyond invasive biopsies: using VASARI MRI features to predict grade and molecular parameters in gliomas

Radiosynthesis and biological evaluation of [18F]AG-120 for PET imaging of the mutant isocitrate dehydrogenase 1 in glioma

Molecular imaging of IDH-mutant gliomas in the new era of IDH inhibitors: preparing for future challenges

Contact Info

Product

Resources

About