. 2018 Sep;139(2):399-409.

doi: 10.1007/s11060-018-2877-6. Epub 2018 Apr 20.

¹⁸F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study

Chirag B Patel^{1

2}, Elisa Fazzari^{1

2}, Ararat Chakhoyan^{3

4}, Jingwen Yao^{3

4}, Catalina Raymond^{3

4}, Huytram Nguyen^{1

2}, Jasmine Manoukian^{1

2}, Nhung Nguyen^{1

2}, Whitney Pope^{3

4}, Timothy F Cloughesy^{1

2}, Phioanh L Nghiemphu^{1

2}, Johannes Czernin⁵, Albert Lai^{1

2}, Benjamin M Ellingson^{6

7

8

9}

Affiliations

¹ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
² UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁴ Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁶ UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
⁷ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
⁸ Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
⁹ Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, 924 Westwood Blvd., Suite 615, Los Angeles, CA, 90024, USA. bellingson@mednet.ucla.edu.

PMID: 29679199
PMCID: PMC6092195
DOI: 10.1007/s11060-018-2877-6

¹⁸F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study

Chirag B Patel et al. J Neurooncol. 2018 Sep.

. 2018 Sep;139(2):399-409.

doi: 10.1007/s11060-018-2877-6. Epub 2018 Apr 20.

Authors

Affiliations

¹ Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
² UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
³ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁴ Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁶ UCLA Neuro-Oncology Program, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
⁷ UCLA Brain Tumor Imaging Laboratory (BTIL), Center for Computer Vision and Imaging Biomarkers, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
⁸ Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. bellingson@mednet.ucla.edu.
⁹ Departments of Radiological Sciences and Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, 924 Westwood Blvd., Suite 615, Los Angeles, CA, 90024, USA. bellingson@mednet.ucla.edu.

PMID: 29679199
PMCID: PMC6092195
DOI: 10.1007/s11060-018-2877-6

Abstract

Introduction: To report the potential value of pre-operative ¹⁸F-FDOPA PET and anatomic MRI in diagnosis and prognosis of glioma patients.

Methods: Forty-five patients with a pathological diagnosis of glioma with pre-operative ¹⁸F-FDOPA PET and anatomic MRI were retrospectively examined. The volume of contrast enhancement and T2 hyperintensity on MRI images along with the ratio of maximum ¹⁸F-FDOPA SUV in tumor to normal tissue (T/N SUV_max) were measured and used to predict tumor grade, molecular status, and overall survival (OS).

Results: A significant correlation was observed between WHO grade and: the volume of contrast enhancement (r = 0.67), volume of T2 hyperintensity (r = 0.42), and ¹⁸F-FDOPA uptake (r = 0.60) (P < 0.01 for each correlation). The volume of contrast enhancement and ¹⁸F-FDOPA T/N SUV_max were significantly higher in glioblastoma (WHO IV) compared with lower grade gliomas (WHO I-III), as well as for high-grade gliomas (WHO III-IV) compared with low-grade gliomas (WHO I-II). Receiver-operator characteristic (ROC) analyses confirmed the volume of contrast enhancement and ¹⁸F-FDOPA T/N SUV_max could each differentiate patient groups. No significant differences in ¹⁸F-FDOPA uptake were observed by IDH or MGMT status. Multivariable Cox regression suggested age (HR 1.16, P = 0.0001) and continuous measures of ¹⁸F-FDOPA PET T/N SUV_max (HR 4.43, P = 0.016) were significant prognostic factors for OS in WHO I-IV gliomas.

Conclusions: Current findings suggest a potential role for the use of pre-operative ¹⁸F-FDOPA PET in suspected glioma. Increased ¹⁸F-FDOPA uptake may not only predict higher glioma grade, but also worse OS.

Keywords: 18F-FDOPA PET; Biomarker; Glioma; MRI.

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Figures

**Fig. 1. Post-contrast T1-weighted images, T2-weighted turbo spin echo or fluid attenuated inversion recovery (FLAIR) images, and ¹⁸F-FDOPA PET SUV maps for representative patients**
A) 19-year-old female with a World Health Organization (WHO) grade I ganglioglioma. B) 24-year-old female with a WHO grade II diffuse astrocytoma. C) 32-year-old male with WHO grade III anaplastic oligodendroglioma. D) 74-year-old male with WHO IV glioblastoma.

**Fig. 2. Anatomic MRI and ¹⁸F-FDOPA PET measurements in glioma patients**
A) Volume of contrast enhancement, B) volume of T2 hyperintensity, and C) ¹⁸F-FDOPA PET T/N SUV_max ratio comparisons between World Health Organization (WHO) IV glioblastoma (GBM) and lower grade gliomas (WHO I–III). D) Receiver-operator characteristic (ROC) curves illustrating sensitivity and specificity of anatomic MRI and ¹⁸F-FDOPA PET measurements to differentiate WHO IV GBM from lower trade gliomas (WHO I–III). E) Volume of contrast enhancement, F) volume of T2 hyperintensity, and G) ¹⁸F-FDOPA PET T/N SUV_max ratio comparisons between high-grade gliomas (HGG; WHO III–IV) and low-grade gliomas (LGG; WHO I–II). H) ROC curves illustrating sensitivity and specificity of anatomic MRI and ¹⁸F-FDOPA PET measurements in discriminating HGG from LGG.

**Fig. 3. Anatomic MRI and ¹⁸F-FDOPA PET measurements across IDH mutation status and MGMT promoter methylation status**
A) Volume of contrast enhancement, B) volume of T2 hyperintensity, and C) ¹⁸F-FDOPA PET T/N SUV_max ratio comparisons between isocitrate dehydrogenase (IDH) mutant (IDH^MUT) and wild type (IDH^WT) gliomas (n=39 evaluable). D) Volume of contrast enhancement, E) volume of T2 hyperintensity, and F) ¹⁸F-FDOPA PET T/N SUV_max ratio comparisons between O⁶-methylguanine-DNA methyltransferase (MGMT) promoter methylated and unmethylated gliomas (n=33 evaluable).

**Fig. 4. Kaplan-Meier survival curves for composite MRI and ¹⁸F-FDOPA PET index of high-risk glioma patients**
High-risk patients (N=14) were defined as those with volume of contrast enhancement (CE) greater than 1 cc (“measurable tumor”) and ¹⁸F-FDOPA PET T/N SUV_max ratio greater than 1.7 (group median). Results demonstrate a significantly shorter OS in high high-risk patients (*Log-rank, HR = 3.05, P=0.012*).

See this image and copyright information in PMC

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¹⁸F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study

Affiliations

¹⁸F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study

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