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

Clinical article

Yasuyoshi Chiba M.D., Ph.D. 1 , Manabu Kinoshita M.D., Ph.D. 1 , Yoshiko Okita M.D., Ph.D. 1 , Akihiro Tsuboi M.D., Ph.D. 2 , Kayako Isohashi M.D., Ph.D. 3 , Naoki Kagawa M.D., Ph.D. 1 , Yasunori Fujimoto M.D., Ph.D. 1 , Yusuke Oji M.D., Ph.D. 4 , Yoshihiro Oka M.D., Ph.D. 5 , Eku Shimosegawa M.D., Ph.D. 3 , Satoshi Morita Ph.D. 6 , Jun Hatazawa M.D., Ph.D. 3 , Haruo Sugiyama M.D., Ph.D. 7 , Naoya Hashimoto M.D., Ph.D. 1 and Toshiki Yoshimine M.D., Ph.D. 1
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  • 1 Departments of Neurosurgery;
  • 2 Cancer Immunotherapy;
  • 3 Nuclear Medicine and Tracer Kinetics;
  • 4 Cancer Stem Cell Biology;
  • 5 Respiratory Medicine, Allergy, and Rheumatic Diseases; and
  • 7 Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka; and
  • 6 Department of Biostatistics and Epidemiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan
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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.

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Contributor Notes

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.

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