Use of 11C-methionine PET parametric response map for monitoring WT1 immunotherapy response in recurrent malignant glioma

Clinical article

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Object

Immunotherapy targeting the Wilms tumor 1 (WT1) gene product is a promising treatment modality for patients with malignant gliomas, and there have been reports of encouraging results. It has become clear, however, that Gd-enhanced MR imaging does not reflect prognosis, thereby necessitating a more robust imaging evaluation system for monitoring response to WT1 immunotherapy. To meet this demand, the authors performed a voxel-wise parametric response map (PRM) analysis of 11C-methionine PET (MET-PET) in WT1 immunotherapy and compared the data with the overall survival after initiation of WT1 immunotherapy (OSWT1).

Methods

Fourteen patients with recurrent malignant glioma were included in the study, and OSWT1 was compared with: 1) volume and length change in the contrast area of the tumor on Gd-enhanced MR images; 2) change in maximum uptake of 11C-methionine; and 3) a more detailed voxel-wise PRM analysis of MET-PET pre- and post-WT1 immunotherapy.

Results

The PRM analysis was able to identify the following 3 areas within the tumor core: 1) area with no change in 11C-methionine uptake pre- and posttreatment; 2) area with increased 11C-methionine uptake posttreatment (PRM+MET); and 3) area with decreased 11C-methionine uptake posttreatment. While the results of Gd-enhanced MR imaging volumetric and conventional MET-PET analysis did not correlate with OSWT1 (p = 0.270 for Gd-enhanced MR imaging length, p = 0.960 for Gd-enhanced MR imaging volume, and p = 0.110 for MET-PET), the percentage of PRM+MET area showed excellent correlation (p = 0.008) with OSWT1.

Conclusions

This study describes the limited value of Gd-enhanced MR imaging and highlights the potential of voxel-wise PRM analysis of MET-PET for monitoring treatment response in immunotherapy for malignant gliomas. Clinical trial registration no.: UMIN000002001.

Abbreviations used in this paper:GBM = glioblastoma multiforme; MET-PET = 11C-methionine PET; OSWT1 = overall survival after initiation of Wilms tumor 1 immunotherapy; PRM = parametric response map; RECIST = Response Evaluation Criteria in Solid Tumors; ROI = region of interest; WT1 = Wilms tumor 1.

Article Information

Address correspondence to: Manabu Kinoshita, M.D., Ph.D., Department of Neurosurgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. email: m-kinoshita@nsurg.med.osaka-u.ac.jp.

Please include this information when citing this paper: published online January 13, 2012; DOI: 10.3171/2011.12.JNS111255.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Image processing procedures. 11C-methionine PET data obtained before and 12 weeks after WT1 immunotherapy initiation were fused and registered onto conventional contrast-enhanced MR images. All 3 images were converted into a 256 × 256 × 256, 1-mm isotropic image matrix. Post-WT1 11C-methionine uptake was plotted as a function of pre-WT1 11C-methionine uptake. After calculating the linear regression line with the ± 2 SD distribution range in contralateral normal brain tissue, an ROI was set at the contrast-enhanced pre-WT1 immunotherapy lesion. The obtained plots were categorized into the following 3 areas: 1) area of no change in 11C-methionine uptake pre- and posttreatment, 2) area with increased 11C-methionine uptake posttreatment (PRM+MET), and 3) area with decreased 11C-methionine uptake posttreatment (PRM−MET). These areas were reconstructed in images for visual inspection (PRM+MET in red and PRM−MET in blue).

  • View in gallery

    Case 2. A representative treatment responder with recurrent GBM (OSWT1 144.7 weeks). Images were analyzed as in Fig. 1. Voxel-wise PRM analysis revealed that most of the contrast-enhanced lesion was within the PRM−MET area. Although the OSWT1 was 144.7 weeks, conventional MR imaging evaluated the response as progressive disease. Gd-MRI = Gd-enhanced MR imaging; T/Nr = T/N max.

  • View in gallery

    Case 7. A representative treatment nonresponder with recurrent GBM (OSWT1 20.9 weeks). Images were analyzed as in Fig. 1. Voxel-wise PRM analysis revealed that most of the contrast-enhanced lesion was within the PRM+MET area, suggesting that the patient was not responsive to WT1 immunotherapy.

  • View in gallery

    Correlation of OSWT1 with changes in tumor length and volume using contrast-enhanced MR imaging and the T/N max of MET-PET. Correlations between OSWT1 and changes (from before WT1 immunotherapy to 12 weeks after immunotherapy initiation) on Gd-enhanced MR imaging–measured tumor length (A), volume (B), and T/N max of MET-PET (C) are presented. The correlations were not statistically significant (p = 0.270, 0.960, and 0.110, respectively; 14 cases).

  • View in gallery

    Correlation of OSWT1 with PRM−MET and PRM+MET. Correlations between OSWT1 and percentage areas of PRM−MET (left) and PRM+MET (right) are presented. The percentage of PRM+MET within the contrast-enhanced lesion before WT1 immunotherapy initiation correlated best with OSWT1 (p = 0.008; 14 cases).

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