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

J Neurosurg. 2012 Apr;116(4):835-42. doi: 10.3171/2011.12.JNS111255. Epub 2012 Jan 13.

Abstract

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 (11)C-methionine PET (MET-PET) in WT1 immunotherapy and compared the data with the overall survival after initiation of WT1 immunotherapy (OS(WT1)).

Methods: Fourteen patients with recurrent malignant glioma were included in the study, and OS(WT1) 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 (11)C-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 (11)C-methionine uptake pre- and posttreatment; 2) area with increased (11)C-methionine uptake posttreatment (PRM(+MET)); and 3) area with decreased (11)C-methionine uptake posttreatment. While the results of Gd-enhanced MR imaging volumetric and conventional MET-PET analysis did not correlate with OS(WT1) (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 OS(WT1).

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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adjuvants, Immunologic
  • Adult
  • Aged
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Cancer Vaccines / administration & dosage*
  • Carbon Radioisotopes*
  • Cell Survival / drug effects*
  • Cell Survival / genetics
  • Female
  • Glioma / diagnostic imaging
  • Glioma / drug therapy*
  • Glioma / genetics
  • Glioma / pathology
  • Humans
  • Image Interpretation, Computer-Assisted*
  • Injections, Intradermal
  • Magnetic Resonance Imaging*
  • Male
  • Mannitol / analogs & derivatives
  • Methionine*
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnostic imaging
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Oleic Acids
  • Positron-Emission Tomography / methods*
  • Radioactive Tracers*
  • Tumor Burden / drug effects
  • WT1 Proteins / drug effects*
  • Young Adult

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Carbon Radioisotopes
  • Oleic Acids
  • Radioactive Tracers
  • WT1 Proteins
  • montanide ISA 51
  • Mannitol
  • Methionine