Joint Program in Nuclear Medicine

PET Imaging in Primary Brain Tumors

Alexander Matthies, MD 
Alan J. Fischman, MD PhD

November 4, 1997

Presentation

A 57 year old male presented with new onset focal seizures and was found to have an about 2 x 2 x 2 cm mass in the high posterior portion of his left parietal lobe (shown on MRI). The patient underwent gross total resection of a glioblastoma multiforme (grade IV in the WHO classification). He was subsequently treated with high dose proton beam radiation resulting in marked clinical improvement. About 8 months later there was deterioration of the previously stable clinical condition and MRI at this time showed increasing extent and degree of gadolineum enhancement, which was thought to represent either radiation necrosis or recurrent tumor.

Imaging Findings

F-18-FDG PET scan revealed an area of moderate tracer uptake at the prior tumor site, suspicious for tumor recurrence. The findings on functional MRI supported this interpretation. A C-11-Methionine PET study showed markedly increased uptake at the prior surgical site and was very suggestive of tumor recurrence. 

Clinical Follow up:

A biopsy performed immediately after the PET scans showed only radiation necrosis. The patient died 9 months later and an autopsy demonstrated tumor recurrence and radiation necrosis.

Discussion

Primary CNS tumors account for about 1-2% of all malignancies. The incidence in 1995 was 10.9 per 100,000. Of these slightly more than 55% were malignant (1). Gliomas account for about 45-50%, meningiomas for about 15% of all primary brain tumors, while all other types are much less common (2).

Initial imaging is usually done with contrast enhanced CT or MRI, which provides excellent information about lesion anatomy. However follow-up of primary brain tumors after surgery, radiation and chemo therapy is often difficult, as CT and MRI are usually not able to differentiate recurrent tumor from radiation necrosis. Contrast enhancement on CT and MRI at the site of the treated and / or excised tumor usually occurs few days after surgery, often increases during the following days / weeks and may persist for several months. Radiation necrosis can also be present, if the enhancement occurs with a delay of several months.

Since the early 80’s PET imaging has been applied - among other indications - for the evaluation of brain tumors before and after treatment.

Indications is this setting include:

The most frequently applied radiotracers include : The first studies of patients with brain tumors, evaluated with PET imaging, were published in the early 80’s by the neuro imaging group at the NIH (3). They demonstrated the feasibility of brain tumor imaging with FDG PET and showed, that it is more accurate than contrast CT for tumor grading.

Subsequently larger groups of brain tumor patients were evaluated to determine the clinical value of this emerging imaging modality. Di Chiro (4) examined 45 patients with proven high grade brain tumors after surgery, radiation and chemotherapy. Poorly differentiated tumors showed significantly higher glucose metabolism than more differentiated ones. The calculation of the ratio of metabolic values (tumor compared to the contralateral normal brain parenchyma) revealed that a ratio of greater than 1.4 was associated with a poor prognosis (median survival 5 months), while patients with a ratio of less than 1.4 had a median survival of 19 months. Alavi et al. (5) came to similar conclusions using F-18-FDG PET in 29 patients with primary brain tumors. Of 23 patients with high grade tumors 9 patients with hypometabolic lesions had a 1-year survival of 78%, while the group with hypermetabolic lesions had a 1 year survival of only 29%.

Glantz et al. (6) demonstrated, that FDG PET imaging in brain tumor patients was not only superior to contrast CT in identifying early recurrence, but also a better predictor of outcome than surgical biopsy results. In this study the vast majority of patients (19 of 20) with hypermetabolic lesions in areas of prior resection had early tumor recurrence. All 12 patients with hypometabolic abnormalities revealed radiation necrosis.

In the past few years there has been an increasing number of brain tumor PET studies, that apply positron labeled amino acid analogs. The most significant advantage of these tracers is related to the markedly lower background activity in normal brain tissue compared to FDG. This may enable the detection of smaller tumors (primary or recurrent). However the currently used amino-analog tracer are carbon-11 labeled, which requires an on-site cyclotron because of the short half-life of 20 minutes. Fluorine-18 labeled amino acid analogs are not widely used because of low radiochemical yield.

Uptake of thymidine and tyrosine in brain tumors appears to reflect a combination of break down of the blood brain barrier, amino-acid transport and protein synthesis. In contrast methionine uptake is probably related to membrane transport phenomena, as blockage of protein synthesis does not seem to influence the methionine uptake (7), making this tracer less specific.

Pruim et al. (8) examined 22 brain tumor patients with C-11-Tyrosine and determined a sensitivity of 92% and specificity of 87% for the tumor detection. However there was no definite correlation between protein synthesis rate and tumor grade.

Conclusion:

PET imaging of brain tumors with FDG is helpful in stratifying patients and detection of early tumor recurrence following surgery and radiation/ chemotherapy. A disadvantage is the relative high background due to normal gray matter glucose utilization, that can conceal small amounts of tumor tissue. Furthermore intense focal inflammation can lead to a false positive scan as recently reported by Fischman et al. (9) in a patient with atypical meningioma and enlarging areas of enhancement on MRI 18 months after treatment of the original tumor.

Positron labeled amino acid analogs have in general a low back ground uptake in gray and white matter, which allows easier detection of tumors (especially small ones). However with this group of tracers no definite correlation between uptake and tumor grade was demonstrated.

References

1.) Central brain tumor registry of the USA, 1995 Annual Report (1996)

2.) Anne Osborne: “Diagnostic Neuroradiology”, Mosby Press Group

3.) Patronas et al.: “18F-Fluorodeoxyglucose and emission tomography in the evaluation of radiation necrosis of the brain” Radiology 1982; 144: 885 - 889

4.) De Chiro et al.: “Positron Emission Tomography using (18F) Fluoro-deoxy-glucose in Brain Tumors. A powerful diagnostic and prognostic tool” Invest Radiology 1987; 22: 360 - 371

5.) Alavi et al.: “Positron Emission Tomography in Patients with Glioma. A predictor of Prognosis” Cancer 1988; 62: 1074 - 1078

6.) Glantz et al.: “Identification of Early Recurrence of Primary Central Nervous System Tumors by (18F)Fluorodeoxyglucose Positron Emission Tomography” Annals of Neurology 1991; 29: 347 - 355

7.) Ishiwata et al.: “Re-evaluation of amino-acid PET studies: can the protein synthesis rate in brain and tumor tissue be measured in vivo? J Nucl Med 1993; 34: 1936 - 1943

8.) Pruim et al.: “Brain Tumors: L-(1-C-11) Tyrosine PET for Visualization and Quantification of Protein Synthesis Rate” Radiology 1995; 197: 221 - 226

9.) Fischman et al.: “FDG Hypermetabolism Associated with Inflammatory Necrotic Changes Following Radiation of Meningioma” J Nucl Med. 1997; 38: 1027 - 1029

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J. Anthony Parker, MD PhD, Tony_Parker@bidmc.harvard.edu