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

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.

• Authors: Yasuyoshi Chiba, Manabu Kinoshita, Yoshiko Okita, Akihiro Tsuboi, Kayako Isohashi, Naoki Kagawa, Yasunori Fujimoto, Yusuke Oji, Yoshihiro Oka, Eku Shimosegawa, Satoshi Morita, Jun Hatazawa, Haruo Sugiyama, Naoya Hashimoto, Toshiki Yoshimine
• Journal: Journal of neurosurgery (J Neurosurg) Vol. 116 Issue 4 Pg. 835-42 (Apr 2012) ISSN: 1933-0693 [Electronic] United States
• PMID: 22242671 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

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

Topics

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