Malignancy of intracerebral lesions evaluated with 11C-methionine-PET

doi:10.1016/j.jocn.2005.07.001

Journal of Clinical Neuroscience

Volume 12, Issue 7, September 2005, Pages 775-780

https://doi.org/10.1016/j.jocn.2005.07.001 Get rights and content

Summary

Positron emission tomography (PET) allows examination of a variety of physiological parameter, including blood flow, glucose, amino acid and oxygen metabolism. However, correlation of PET scan findings and the degree of malignancy of intracerebral tumors continues to be controversial.

Nine patients with primarily diagnosed intraparenchymal brain tumors were included in this study. We performed ¹¹C-methionine-PET (met-PET) prior to surgical treatment and the differential absorption ratio (DAR) was calculated. All patients underwent open or stereotactic surgery and specimens for pathological diagnosis were obtained. The biological activity of each tumor was determined by calculation of the proliferation index from MIB-1 immunohistochemistry.

The DAR of met-PET for individual tumors correlated with the histological diagnosis and degree of malignancy and this was further confirmed by good correlation with the MIB-1 proliferation index.

We conclude that met-PET may be a reliable and effective preoperative evaluation to determine the type and malignancy of intraparenchymal brain lesions.

Introduction

Cerebral gliomas are most commonly malignant and despite treatment have a poor prognosis.¹ Some benign intraparenchymal brain lesions, including gliosis or radiation necrosis may mimic glioma in conventional preoperative imaging studies, including CT and MRI scans. Therefore, in order to guide better treatment strategies and avoid unnecessary operations, further information is needed about the pathophysiology of these lesions. Positron emission tomography (PET) allows examination of various physiological parameters. A number of agents have been used in PET studies to evaluate brain tumor blood flow and glucose, amino acid and oxygen metabolism. Among them, ¹⁸F-fluorodeoxygluscose PET (FDG-PET) and ¹¹C-methionine-PET (met-PET) have been reported to correlate with the biological behavior of gliomas.² However, these results remain controversial, particularly in relation to FDG-PET. Some astrocytomas are iso- or even hypometabolic to brain on FDG-PET.³ Met-PET has been shown to be superior to FDG-PET in defining the grade of astrocytoma.⁴ However, reports are conflicting and some authors report that met-PET cannot successfully predict the histological grade of gliomas.⁵ The controversy is, to some extent, due to the lack of objective means to measure the correlation between met-PET and the biological behavior of individual lesions. We believe that further studies must be done to evaluate the reliability of met-PET as a predictor of the biological behavior of individual intraparenchymal lesions. Thus, we chose an objective, quantitative method to predict the biological activity of each tumor by determining the proliferation index with MIB-1 immunostaining and compared the results of met-PET with the MIB-1 proliferation index in intraparenchymal lesions. This has not been previously reported in the literature.

Section snippets

Materials and methods

Nine patients with primarily diagnosed intraparenchymal brain tumors were included in this prospective study. All patients had a met-PET scan prior to any treatment. A 10 min scan was performed 30 min after the injection of 5–15 mCi of the tracer (¹¹C-methionine), and the degree of radioactivity was expressed as the differential absorption ratio (DAR). The region from which the DAR was calculated was visually selected from met-PET scans showing the best demarcation of the tumor and the highest

Results

The histological diagnosis was gliosis (3 cases), glioblastoma (2 cases), and oligodendroglioma, low grade astrocytoma, anaplastic astrocytoma and metastatic transitional cell carcinoma in one case each.

The met-PET DAR correlated well with the pathological diagnosis. The DAR of the 3 cases of gliosis ranged from 3.6 to 5.3 and the MIB-1 PI was 0–1.7% (Fig. 1). The met-PET DAR of the two low-grade gliomas was 9.6 and 9.8 and the MIB-1 PI was 1.7 and 2.9% respectively (Fig. 2). The met-PET DAR of

Discussion

Despite advances in neurosurgical treatment and sophisticated radio- and chemotherapy, satisfactory outcomes have not yet been achieved in glioma patients.¹ To plan better treatment strategies, preoperative understanding of the biological activity of individual tumors is important. However, both CT and MRI have deficiencies in this regard. Additionally, both CT and MRI can misinterpret non-neoplastic lesions as tumor. The 3 cases of gliosis in this series were all misdiagnosed as tumors

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Cited by (11)

Comparative preoperative evaluation of 18F-FDG and 18F-DOPA PET in 43 grade II and III gliomas: Correlation with histological and molecular characteristics
2016, Medecine Nucleaire
Caractériser et comparer l’information biologique apportée par le 18F-FDG et la 18F-FDOPA, analysés séparément puis conjointement, en relation avec les facteurs pronostiques, notamment histologiques et moléculaires dans le bilan préopératoire des gliomes de grade II et III.
Quarante-trois patients ayant bénéficié d’une TEP au 18F-FDG et à la 18F-FDOPA dans le bilan préopératoire de gliome ont été rétrospectivement inclus (35 gliomes de grade II et 8 grade III). Les captations tumorales en 18F-FDG et en 18F-FDOPA étaient déterminées en utilisant des méthodes qualitatives pour le 18F-FDG et semi-quantitatives pour la 18F-FDOPA (ratio tumeur/striatum), puis étaient comparées aux caractéristiques cliniques (âge, sexe), chirurgicales (type de chirurgie, localisation tumorale), histologiques et immuno-histochimiques (histologie, grade, index Ki-67) et moléculaires (mutation IDH, codélétion 1p19q, mutation de la protéine p53 et statut « triple négatif »). Pour analyser l’impact relatif des deux radiotraceurs, nous avons divisé les patients en fonction des différentes combinaisons possibles des résultats des TEP au 18F-FDG et à la 18F-FDOPA pour créer 3 groupes : groupe −/−, groupe −/+ et groupe +/+ que nous avons comparés 2 à 2.
Une captation en 18F-FDG positive était associée à un index de prolifération Ki-67 plus élevé (p = 0,021). En utilisant le ratio tumeur/striatum, une captation 18F-FDOPA plus élevée était associée à la présence d’une mutation IDH (p = 0,037) et d’une codélétion 1p19q (p = 0,030). Il existait une corrélation positive entre l’index Ki-67 et le ratio tumeur/striatum (r = 0,33, p = 0,029). En comparant le groupe −/− et le groupe −/+ la codélétion 1p19q était plus fréquemment présente dans le groupe −/+ que dans le groupe −/− (p = 0,027). Il en était de même pour la mutation IDH (p = 0,028). En comparant le groupe −/− et le groupe +/+, il y avait dans le groupe −/− plus de gliomes présentant un index Ki-67 moins élevé (p = 0,038).
La TEP au 18F-FDG et à la 18F-FDOPA apportaient toutes deux séparément des informations sur la prolifération cellulaire. La TEP à la 18F-FDOPA pourrait apporter des informations supplémentaires sur le versant moléculaire. Enfin, l’association de la TEP au 18F-FDG et à la 18F-FDOPA pourrait permettre de renseigner sur la prolifération cellulaire ainsi que sur la présence d’une codélétion 1p19q et d’une mutation IDH.
To characterize and compare the biological information brought by 18F-FDG and 18F-FDOPA, analyzed separately and together, in relation with prognostic factors including histological and molecular factors in the preoperative assessment of grade II and III gliomas.
Forty-three patients who underwent 18F-FDG and 18F-FDOPA PET in the preoperative assessment of glioma have been retrospectively included (35 grade II and 8 grade III). 18F-FDG and 18F-FDOPA uptakes were determined using qualitative method for 18F-FDG and semi-quantitative method for 18F-FDOPA (tumor/striatum ratio), and were compared with demographic (age, sex), surgical (type of surgery, localization) histological, immunohistochemistrical (histology, grade, Ki-67 index) and molecular characteristics (IDH mutation, 1p19q codeletion, p53 mutation and “triple negative” status). To analyze the relative impact of the two radiopharmaceuticals, we have divided the patients according to the different possible combinations of 18F-FDG and 18F-FDOPA PET to create 3 groups: group −/−, group −/+ and group +/+.
A positive 18F-FDG uptake was associated with a higher Ki-67 index (P = 0.021). Using tumor/striatum ratio, a higher 18F-FDOPA uptake was associated with presence of IDH mutation (P = 0.037) and presence of 1p19q codeletion (P = 0.030). There was a positive correlation between Ki-67 index and tumor/striatum ratio (r = 0.33; P = 0.029). Comparing group −/− and group −/+, there was more frequently presence of 1p19q codeletion in group −/+ than in group −/− (P = 0.008). The same applies to IDH mutation (P = 0.028). Comparing group −/− and group +/+, there were more frequently a lower Ki-67 index (P = 0.006) in group −/−.
The two 18F-FDG and 18F-FDOPA PET brought separately information about cellular proliferation. 18F-FDOPA PET could bring additional information on the molecular side of the tumor. Finally, the association between 18F-FDG and 18F-FDOPA PET could give more information about cellular proliferation and presence of 1p19q codeletion and IDH mutation.
Carbon 11-labeled methionine positron emission tomography for detection of residual viable tumor cells after adjuvant therapy in nongerminomatous malignant germ cell tumors in 2 cases including an autopsy case
2009, Surgical Neurology
Citation Excerpt :
Carbon 11–labeled methionine positron emission tomography studies, on the other hand, have shown that it is not only an excellent method for monitoring active tumor tissues, but it also provides information on the biological nature of the tumor cells. In addition, MET-PET findings have led to the development of powerful protocols for tumor therapy [2,10,12]. We used MET-PET to assess the persistence of viable tumor cells in patients with NGMGCT who had undergone adjuvant therapy and found that, in the event viable tumor cells are present, resection of the residual mass might be helpful for better outcome and prognosis.
The treatment of intracranial NGMGCTs is generally based on chemotherapy and radiotherapy. To avoid the potential of tumor recurrence, we normally have the residual mass lesion removed after adjuvant therapy. However, since 1988 we have treated 15 patients with NGMGCT and pathologically evaluated 12 such patients after adjuvant therapy by a new method we have developed and found viable tumor cells in 4 (33%) of 12 patients. Based on our experience, therefore, we feel we have been able to develop a reliable diagnostic tool for confirming the presence or absence of viable tumor cells in residual mass after adjuvant therapy for patients with NGMGCT.
We describe here 2 patients with NGMGCTs who underwent MET-PET. Patient 1 was an 11-year-old boy with immature teratoma. On gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), a high-intensity area was found in his right cerebellar hemisphere and a high uptake in MET-PET was confirmed in the same region. We judged it as the recurrence of the tumor. Finally, he died and was autopsied. Patient 2 was a 16-year-old girl with an NGMGCT who received combined chemo- and radiotherapy that led to a reduction in the volume of the tumor. Her serum β-HCG and HCG levels also returned to the reference range. However, the mass did not disappear and another MRI scan disclosed a residual Gd-enhanced lesion. To assess whether there were residual viable tumor cells, MET-PET was performed, and it demonstrated no hyper-uptake region in the residual mass. We, therefore, did not surgically remove the mass and kept the patient under observation. There has not been any tumor recurrence in this patient for more than 2 years.
In these 2 cases, the increased MET uptake was more specific of tumor tissue and more accurate than MR Gd enhancement. MET-PET may be a useful diagnostic tool for predicting viable tumor cells after adjuvant therapy in patients with NGMGCT, thus allowing further surgical intervention.
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^☆: This paper was supported by a grant from the National Science Council. Grant number: NSC86-2314-B075-004.

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Clinical studyMalignancy of intracerebral lesions evaluated with 11C-methionine-PET☆

Summary

Introduction

Section snippets

Materials and methods

Results

Discussion

Surg Neurol

PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids

J Comput Assist Tomogr

Brain tumor protein synthesis and histological grades: a study by positron emission tomography with C11-L-methionine

J Neurooncol

Usefulness of 11C-met PET in the evaluation of brain lesions that are hypo- or isometabolic on 18F-FDG PET

Eur J Nucl Med Mol Imaging

11C-L-methionine uptake in gliomas

Neurosurg

Positron emission tomography using 18F-fluorodeoxyglucose in brain tumors, a powerful diagnostic and prognostic tool

Invest Radiol

Glucose utilization of cerebral gliomas measured by 18F-fluorodeoxyglucose and positron emission tomography

Neurology

Immunohistological detection of tumor growth fraction (Ki-67 antigen) in formalin-fixed and routinely processed tissue

J Pathol

FDG-PET as a prognostic indicator in radiochemotherapy of glioblastoma

J Comput Assist Tomogr

Prognostic significance of Ki-67 proliferation index in supratentorial fibrillary astrocytic neoplasms

J Neurosurg

Clinical study
Malignancy of intracerebral lesions evaluated with ¹¹C-methionine-PET☆

¹¹C-L-methionine uptake in gliomas

Positron emission tomography using ¹⁸F-fluorodeoxyglucose in brain tumors, a powerful diagnostic and prognostic tool

Glucose utilization of cerebral gliomas measured by ¹⁸F-fluorodeoxyglucose and positron emission tomography