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Position of nuclear medicine techniques in the diagnostic
work-up of brain tumors
A. DEL SOLE 1, R. MONCAYO 2, G. TAFUNI 3, G. LUCIGNANI 1, 4
Although any patient with a suspected brain tumor,
either primary or metastatic, should be studied with
anatomic imaging modalities such as angiography, computerized tomagraphy (CT) or magnetic resonance imaging (MRI), nuclear medicine techniques are available to
further characterize some biological features of brain
lesions and help in diagnosis and therapy planning.
Bloob-brain-barrier disruption can be easily assessed
with single-photon emission tomography (SPET), whereas focal metabolic changes can be better demonstrated
by positron emission tomography (PET) as specific
radiopharmaceuticals are available to detect changes in
glucose utilization and aminoacid uptake with this technique. Expression of specific tumoral antigens is the
basis of imaging with radioimmunoscintigraphy, a
promising technique that can be applied to brain tumor
therapy. The major clinical applications of nuclear medicine in the study of brain tumors — evaluation of the
extension of a tumoral mass, differential diagnosis and
evaluation of therapy and prognosis — are discussed.
KEY WORDS: Brain neoplasms - Nuclear medicine Tomography, emission computed - Tomography, emission
computed, single photon.
I
ntracranial brain neoplasms can be classified into
primary brain tumors and metastatic tumors.
Metastatic brain tumors are more common than primary brain tumors and are associated with lung neoplasms as well as breast, gastrointestinal, genitourinary
tumors and melanomas.
The basic classification of primary brain tumors by
the World Health Organization (WHO) relies on their
Address reprint requests to: Prof. G. Lucignani, Unit of Molecular
Imaging, Department of Radiation Oncology, European Institute of
Oncology, Via Ripamonti 435, 20141 Milano. E-mail: giovanni.luciniani
@unimi.it.
76
1 Institute
of Radiological Sciences, University of Milan, Italy
2 University of Innsbruck, Innsbruck, Austria
3 IRCCS Ospetabe Maggiore Hospital,
Polyclinic of Milan, Italy
4 Unit of Molecular Imaging,
Department of Radiation Oncology
European Institute of Oncology, Milan, Italy
cellular origin, the clinical course and histological
appearance of the neoplasms, immunophenotypic
features and molecular/cytogenetic profile (Table I).1
Primary brain neoplasms which derive from neuroectoderm (primitive neuroectodermal tumor, PNET)
are the most common, followed by tumors of
meningeal, hematopoietic and nerve sheath origin.
In adults the most frequent PNETs derive from glial
cells (astrocyte, oligodendrocyte, ependymocytes and
subependymocytes).
In the Western world, the incidence of primary
brain tumors depends on age and ranges between
1-10 cases/100 000 persons per year (age standardised). The distribution of tumor types for children
and adults differs. In adults it is more frequent to find
pituitary tumors, meningiomas, and glioblastomas. In
children primitive neuroectodermal tumors, astrocytomas and pilocytic astrocytomas can be found.
Non-nuclear medicine diagnostic procedures
Most clinical manifestations of brain tumors are due to
the “mass effect” of the growing tumor and can be
detected when the tumor reaches the size of about 40 g.
They consist of herniation syndromes, progressive
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DEL SOLE
POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMORS
TABLE I.—Revised classification of primary intracranial tumors according to WHO.
Tumors of neuroepithelial tissue
Astrocytic tumors, oligodendroglial tumors, mixed gliomas,
ependymal tumors, choroid plexus tumors, glial tumors of uncertain
origin, neuronal and mixed neuronal-glial tumors, neuroblastic tumors,
pineal parenchyma, embryonal tumors
Tumors of peripheral nerves
Schwannoma, neurofibroma, perineuroma, malignant peripheral nerve
sheath tumors
Tumors of the meninges
Tumors of meningothelial cells, mesenchymal non-meningothelial tumors,
primary melanocytic lesions, tumors of uncertain histogenesis
Lymphomas and hematopoietic neoplasms
Malignant lymphoma, plasmacytoma, granulocytic sarcoma
Germ cell tumors
Germinoma, embryonal carcinoma, Yolk sac tumors, chorioncarcinoma,
teratoma, mixed germ cell tumors
Tumors of the sellar region
Craniopharyngioma (adamantinomatous, papillary), granular cell tumor
alterations of mentation and personality, headache
and seizures. Other focal symptoms depend on the
tumor location and include focal seizures, mental
changes, visual disturbances, speech abnormalities,
motor weakness, sensory disturbances, cranial nerve
signs and gait abnormalities. Computerized tomography (CT) has been the first imaging modality that
could directly visualize the presence of a brain tumor
and is still widely used. Other radiological techniques
have been applied to ascertain the presence of brain
lesions more recently.
Computerized tomography
For many years, CT has been considered the gold
standard in the diagnosis of brain tumors because it
is able to demonstrate the presence of a brain lesion
and define its dimensions and morphology and its
relation with surrounding brain structure. It is also
able to identify perilesional edema and define the
number of brain lesions.
This imaging technique is widely available and is
useful when magnetic resonance imaging (MRI) cannot be used; CT is less degraded by artefacts due to
motion of the patient for the short time of duration of
the exam, but is less sensitive than MRI in brain regions
that are near some bony areas of irregular shape, such
as the posterior fossa and the floor of the middle fossa, due to the presence of beam-hardening artefacts
and can miss non-enhancing tumors such as lowgrade gliomas.
Contrast enhanced computerized tomography
The administration of a contrast agent increases
X-rays attenuation due to the high electron density of
Vol. 48 - No. 2
the iodinated compounds. Contrast enhanced CT can
detect blood-brain-barrier (BBB) disruption that occurs
in many neurological disorders that include acute
stroke, inflammatory and infectious cerebral diseases
and multiple sclerosis. Moreover most brain tumors
directly disrupt the blood-brain-barrier. Themselves,
while in angiogenesis the BBB is absent.
The region of contrast enhancement corresponds
well with the main tumor mass. However, malignant
tumor cells are commonly found beyond the enhanced
portion of the tumor, particularly in gliomas. The type
of enhancement can help in differentiating among
lesions: contrast enhanced CT is still routinely used for
the screening and follow-up of neoplasms. Cerebral
multiple metastases, meningeal carcinomatosis, typical meningiomas or epidermoids can be diagnosed
without further examinations. CT ability to represent
bone structures makes this technique relevant in defining bone destruction or sclerosis associated with
metastatic tumors, pituitary adenomas, meningiomas,
adjacent carcinomas from the sinuses or pharynx, and
in studying lesions with calcific components or localized close to bone structures.
Magnetic resonance imaging
MRI has several advantages as compared to CT.
The technique has a higher contrast resolution and a
lower occurrence of artefacts than CT, associated with
the possibility of 3D-acquisition and reconstruction
and a high spatial definition. These qualities permit an
excellent resolution of brain regions that are poorly
assessed by CT, such as infratentorial, sellar, temporal and meningeal regions. MRI studies are characterised by high sensitivity for structural alterations
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POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMORS
DEL SOLE
caused by tumoral growth, that can further be TABLE II.—Radioisope uptake and histological grade of gliomas.
enhanced by the use of paramagnetic contrast agents.
Grade IV gliomas Grade III gliomas Low-grade tumors
For these reasons, MRI is the procedure of choice for
1.4±1.5
1.04±2
imaging all types of brain tumors. MRI is particularly Thallium index 1.98±3.2
7.6±3.4
0.61±0.83
accurate in establishing the intra- or extra-axial origin BUdR
of tumors; with a better definition it is possible to
detect indirect signs (cortex dislocation, compression
of sulci and cisterns, presence of cleavage plane for
Nuclear medicine diagnostic procedures
extrinsic lesions) and evaluate direct signs of neoNuclear medicine techniques were once used to
plasia. A normal contrast-enhanced MRI scan essenconfirm the presence of a brain mass that was sustially rules out the possibility of a brain tumor.
pected on a clinical basis. Nowadays, morphological
imaging techniques, namely CT and MRI, are usually
Angiography
able to adequately demonstrate the presence of a
The assessment of vascular structure as depicted brain lesion, to define its size and its relation with
by angiography has largely lost its diagnostic role in surrounding brain structures and to identify direct or
the work-up of brain tumors; a relevant exception is indirect signs that can assist in the diagnosis of brain
represented by those lesions that are characterized tumor with a high degree of confidence. Nuclear medby an abnormal angiogenesis, such as hemangioblas- icine methods can assess and quantify biochemical
tomas and meningiomas. At the moment angiogra- parameters in vivo, that are useful to further characphy has a complementary role in the pre-surgical terise brain neoplasms.
assessment of neoplasms, providing information on
the relationships between tumor and vessels. Studies of the blood-brain-barrier and Na/K pump
Angiography is still relevant in the therapeutic phase
Scintigraphic studies aimed at the detection of a
of embolization of meningiomas or base of the skull
leaky
blood-brain-barrier can be useful in a variety of
tumors or intra-arterial chemotherapy for gliomas.
clinical
situations including fever, toxins, and tumors.
The routine use of angio-MR offers the possibility
Without
the disruption of the BBB tracer uptake will
to complete a standard brain MR study adding infornot
occur.
Due to tumor growth, the BBB will be dismation on the relationships existing between tumor
turbed
allowing
tracer uptake. Under these condiand vessels (encasement, venous compressions, etc.).
tions
some
tracers,
like 99mTc-DTPA and 301Tl-chloride
The demonstration of small diameter vessels is still
will
show
a
significant.
But the disruption of BBB is
poor, with a consequent poor definition of tumoral
not
the
only
explanation
of Thallium uptake, as it
angiogenesis, but incoming technical amelioration
accumulates
in
neoplastic
tissues depending upon
will soon widen angio-MR capabilities.
blood-flow, cellular metabolism and efficiency of sodium-potassium ATPase.
Magnetic resonance spectroscopy
Initial studies on comparative tracer uptake in brain
The separation of nuclear resonance frequencies tumors were carried out by Kaplan et al. 2 including
of hydrogen, termed chemical shift, can define a spec- 29 patients with gliomas grade III and IV, of which 7
trum of signals that are a representation of the sever- could be studied post mortem. They found that 201Tl
al chemical forms of hydrogen that are present in the gave the most accurate localization, 67Ga was good if
volume studied. It is a non-invasive approach for the steroids were not being used, while 99mTc-GH could
determination of some cerebral metabolites with clin- not differentiate fibrosis, non-fibrosis, necrosis and
ical relevance, such as membrane phospholipids neoplasma. Similar data were presented by Mountz et
(choline containing compounds) and respective degra- al. 3 An improvement in the technique was the use
dation products, creatine and phosphocreatine (ele- of SPET. In a methodological paper Kim et al. 4
ments of cellular energetic metabolism), N-acetyl described semi-quantitative analysis of the results.
aspartate and N-acetylate groups (marker of neuronal The best analysis method was mean counts in attenpopulation) and lactic acid (marker of hypoxic con- uation-corrected slices. They were able to show that
dition). The technique is relatively insensitive because low-grade tumors had a lower uptake index as comit can only detect compounds that are present in con- pared to high-grade tumors: 1.20±0.40 vs. 2.40±0.61,
centrations of about 1 mM.
respectively.
78
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POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMOURS
A close relationship between Thallium uptake and
proliferative activity was shown by Oriuchi et al. 5
They could demonstrate a positive correlation between
bromodeoxyuridine (BUdR) and the 201Tl uptake
index. Besides the tumor related index values, patients
who died after surgery presented much higher values
than survivors (Table II).
Metabolic studies
Metabolic studies aim at the detection of either
tumor metabolism or of cell proliferation. For tumor
metabolism both glucose utilisation (18F-FDG) and
amino acids uptake (123I-IMT, 124I-IMT and other thyrosine derivatives, or 11C-methionine) can be used.
Tracers for cell proliferation include 124I-deoxy uridine and 11C-2-thymidine. In a similar fashion as
shown for 201Tl and BUdR, 123I-IMT uptake in gliomas
appears to correlate with cellular density (light
microscopy) and proliferative activtiy (Ki-67 nuclear
antigen). Uptake indices for 123I-IMT are higher in
cases of tumor recurrence as compared to patients
without recurrence. Also 99mTc-SestaMIBI and 99mTcTetrofosmin concentrate in hypermetabolic processes such as tumors.
STUDIES OF GLUCOSE METABOLISM
Glucose utilization in tumors can be assessed using
2-[18F]Fluoro-2-deoxy-D-glucose (18F-FDG), which differs from glucose only for the replacement of an
hydroxyl group with radioactive fluorine. Both
18F-FDG and glucose share the same carriers between
the blood-brain-barrier. The accumulation of 18F-FDG,
as detected by PET, is in proportion to glucose metabolic rate of the studied organ. It is well established
that brain neoplasms present an increased glucose
utilization respect to normal tissue, due to a high rate
of glucose degradation into lactic acid even in presence of oxygen. Moreover, an over-expression of
GLUT1 and GLUT3, members of the hexose transporter family, has been observed in several brain
tumor types.
18F-FDG is able to identify the elevated glucose
consumption in brain tumors, and it is now accepted
that the uptake of the tracer correlates with the grade
of malignancy of astrocytic tumors and also in oligodendrogliomas and gangliogliomas.6-8 On the other
hand, low-grade gliomas are not easily identified or
may appear as cold spots surrounded by normal high
uptaking cerebral cortex, hampering a clear definition of tumor extension.
Vol. 48 - No. 2
STUDIES OF AMINO ACIDS UPTAKE
Imaging with radiolabeled amino acids visualizes
protein synthesis and amino acid transport, which
are accelerated in tumors. Methionine and other large
neutral amino acids, are normally supplied to the
brain from protein breakdown and diet through a
transport system in the BBB; because the amino acids
uptake in macrophages and other inflammatory cells
is low, these tracers might be more tumor specific
than 18F-FDG and difficult differential diagnoses with
other cerebral pathologies, i.e., infections, radiation
necrosis, edema, that may cause abnormal 18F-FDG
uptake, can be avoided by using 11C-methionine
(MET). 11C-methionine allows a earlier and more accurate delineation of the extension of the tumor boundaries than contrast-enhanced CT or MRI and is superior than 18F-FDG in delineating low-grade gliomas.9, 10
The use of 11C-methionine is justified by its relatively
simple synthesis, rapid uptake in tumors and clearance
from blood and other tissues. Other amino acids used
for brain tumor imaging are tyrosine, thymidine, glutamate, phenylalanine and their labeled derivatives.
Tyrosine uptake in brain tumors can be assessed with
its labeled derivatives: O-(2-[18F]-fluoroethyl)-L-tyrosine
(18F-FET), L-[3-18F]-a-methyltyrosine (18F-FMT), [123I]iodo-α-methyltyrosine (123I-IMT). Also the uptake of
tyrosine labeled derivatives is higher in brain tumors
than in normal brain tissue. Other labeled amino acids
for the evaluation of brain tumors include [18F]-fluorophenylalanine that has a marked uptake in oligodendrogliomas.
Radioimmunoscintigraphy
Some researchers have tested the feasibility of using
monoclonal antibodies directed against neuroblastoma antigens, epidermal growth factor receptor, placental alcaline phosphatase, di-sialoganglioside GD2
and tenascin. A more elaborated construction has
been reported using 99mTc-PnAO-Biotin together with
an anti-tenascin antibody. More complex techniques
have been proposed to enhance the signal-to-noise
ratio, to overcome the limitations deriving from low
tumor/non-tumor ratio and high dosimetry from the
use of MoAbs directly labeled with Iodine-131. This
technique has a good accuracy for the in vivo immunodetection of gliomas.11
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POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMOURS
DEL SOLE
TABLE III.—Role of various imaging modalities in different clinical settings in the work-up of primary brain tumors.
Clinical
question
Imaging
modality
of choice
CT and MRI
Nuclear
medicine
Diagnosis
of primary
tumor
Differential
diagnosis
Biological
characterisation
Pathology
Treatment
CT and MRI
with
contrast
agent
CT and MRI
with contrast
agent
CT and MRI
with contrast
agent
Refer to
table in the
text
Neurosurgery
radiation
chemotherpy
In AIDS
patients:
FDG-PET or
201Tl-SPET
FDG-PET
or MET-PET;
if not available, 99mTcSestaMIBI or
201Tl-SPET
Clinical indications
Table III summarizes the role of various neuroimaging modalities in different clinical settings in
patients with brain neoplasms.
Identification of a brain tumor
A direct sign of the presence of a brain tumor is the
detection of an area with a density CT or MRI signal different from that of normal cerebral tissue, including
changes secondary to contrast media infusion. Such
changes are secondary to the structural features of
neoplasms. Three main variables differentiate tumors
from normal tissue: water content (due to the increased
cellularity and interstitial fluids, that is, the cytotoxic
intratumoral edema), regressive events (cysts, necrotic and hemorrhagic areas, calcifications, fat degenerative areas), vascular architecture (a feature of most
tumors). Mass effect, edema and bone modifications are
all indirect signs that can help in brain tumor detection.
By combining direct and indirect signs, with intravenous contrast enhancement, brain tumor detection
occurs with almost 100% accuracy with MRI.
For these reasons, anatomical imaging procedures
have become essential tools for brain tumor diagnosis. No patient presenting with symptoms suggesting
the presence of a brain tumor can be assessed properly unless an X-ray CT and/or an MRI scan, with and
without the administration of contrast agents and different acquisition sequences, in case of MRI, is performed.
80
Follow-up
of the treated
patients (clinically
free from
disease)
In
asymptomatic patients:
CT and MRI
with contrast
agent every
3 months,
alternating
Restaging
In
symptomatic
patients: CT
or MRI with
contrast
agents and
FDG-PET or
MET-PET or
(if PET not
available)
99mTcSestaMIBI or
201Tl-SPET
Monitoring
of treatment
response
CT or MRI
with contrast
agent and
FDG-PET or
MET-PET or
(if PET not
available)
99mTcSestaMIBI or
201Tl-SPET
Evaluation of the extension of the disease
An accurate definition of the tumor boundaries is
requested to plan an aggressive surgical treatment
that should spare critical brain structures, such as the
language areas. 11C-methionine is able to detect brain
tumors boundaries, both in primary lesion and recurrence, with a high accuracy, regardless of their pathological grading.12 Also 201Tl and 123I-α-metyl-tyrosine
can be used in this situation, but the limited spatial resolution of the SPET technique may restrict their value in the assessment of the extension of the disease.
Differential diagnosis
Differential diagnosis between brain tumors and
benign lesions is usually based on clinical presentation, laboratory tests and different presentation in CT
and MRI images. In AIDS patients, toxoplasmosis and
primary intracerebral non-Hodgkin’s B cell lymphoma
are both common and clinical presentation and laboratory tests are not useful to establish a correct diagnosis. In this setting, 201Tl can be helpful to demonstrate the presence of a malignant lesion as a focal
accumulation of this tracer at the site of CT/MRI
abnormality strongly suggests lymphoma, while the
absence of uptake of 201Tl allows to exclude the diagnosis of lymphoma with a high degree of confidence.13
Guide for biopsy
High grade brain tumors are characterised by the
presence of an heterogeneous cellular composition for
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POSITION OF NUCLEAR MEDICINE TECHNIQUES IN THE DIAGNOSTIC WORK-UP OF BRAIN TUMOURS
the combination of active disease, non-specific inflammation, necrosis and edema. Both 18F-FDG and 11CMET can be used in the sterotactic environment to
identify the areas of anaplasia or infiltration when a
diagnostic biopsy is to be performed, in an effort to
include the most malignant tissue in the pathologic
specimen.14, 15
Follow-up
EARLY ASSESSMENT OF THERAPY
The assessment of presence of residual tumoral
mass by means of CT or MRI is difficult in the early
phase after surgical or radiant therapy, due to inflammatory reaction. 18F-FDG can differentiate residual
tumor from the effect of therapy and a decline in 18FFDG uptake in a tumor weeks or months after therapy suggests a good response, indicating a reduced
number of viable cells or reduced metabolism of damaged cells.16
LONG-TERM FOLLOW-UP
Even several months after irradiation or chemotherapy for brain tumors, MRI and CT cannot easily distinguish tumor progression from radiation injury or
necrosis. In high-grade tumors with elevated 18F-FDG
uptake before treatment, focal uptake of 18F-FDG in
areas of BBB breakdown detected by CT or MRI suggests the presence viable tumor cells, while absent
FDG uptake suggests that necrosis is present.17
In low-grade gliomas, malignant transformation to
high-grade tumors after treatment is not infrequent.
The detection of areas of increased 18F-FDG uptake in
histologically proven low-grade glioma predicts malignant transformation in such cases.
PROGNOSIS
In high-grade gliomas, the most powerful predictor
of survival is pathological grading. In low-grade
gliomas, the presence of areas of increased 18F-FDG
uptake predicts, in most cases, a worse prognosis.
Experience with other tracers is still limited, but a
low uptake of 11C-methionine in the baseline study is
associated with a longer survival.
Vol. 48 - No. 2
References
1. Smirniotopoulos JG. The new WHO classification of brain tumors.
Neuroimaging Clin N Am 1999;9:595-613.
2. Kaplan WD, Takvorian T, Morris JH, Rumbaugh CL, Connolly BT,
Atkins HL. Thallium-201 brain tumor imaging: a comparative study
with pathologic correlation. J Nucl Med 1987;28:47-52.
3. Mountz JM, Stafford SK, McKeever PE, Taren J, Beierwaltes WH.
Thallium-201 tumor/cardiac ratio estimation of residual astrocytoma. J Neurosurg 1988;68:705-9.
4. Kim KT, Black KL, Marciano D, Mazziotta JC, Guze BH, Grafton S
et al. Thallium-201 SPECT imaging of brain tumors: methods and
results. J Nucl Med 1990;31:965-9.
5. Oriuchi N, Tamura M, Shibazaki T, Ohye C, Watanabe N, Tateno
M et al. Clinical evaluation of thallium-201 SPECT in supratentorial gliomas: relationship to histologic grade, prognosis and proliferative activities [see comments]. J Nucl Med 1993;34:2085-9.
6. Kim CK, Alavi JB, Alavi A, Reivich M. New grading system of cerebral gliomas using positron emission tomography with F-18 fluorodeoxyglucose. J Neuro-Oncol 1991;10:85-91.
7. Mineura K, Shioya H, Kowada M, Ogawa T, Hatazawa J, Uemura
K. Blood flow and metabolism of oligodendrogliomas: a positron
emission tomography study with kinetic analysis of 18F-fluorodeoxyglucose. J Neuro-Oncol 1999;43:49-57.
8. Kincaid PK, El-Saden SM, Park SH, Goy BW. Cerebral gangliogliomas: preoperative grading using FDG-PET and 201Tl-SPECT.
AJNR Am J Neuroradiol 1998;19:801-6.
9. Derlon JM, Petit-Taboue MC, Chapon F, Beaudouin V, Noel MH,
Creveuil C et al. The in vivo metabolic pattern of low-grade brain
gliomas: a positron emission tomographic study using 18F-fluorodeoxyglucose and 11C-L-methylmethionine. Neurosurgery
1997;40:276-87.
10. Kaschten B, Stevenaert A, Sadzot B, Deprez M, Degueldre C, Del
Fiore G et al. Preoperative evaluation of 54 gliomas by PET with
fluorine-18-fluorodeoxyglucose and/or carbon-11-methionine. J
Nucl Med 1998;39:778-85.
11. Paganelli G, Magnani P, Zito F, Lucignani G, Sudati F, Truci G et
al. Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of
[99mTc]PnAO-biotin. Eur J Nucl Med 1994;21:314-21.
12. Ogawa T, Inugami A, Hatazawa J, Kanno I, Murakami M, Yasui N
et al. Clinical positron emission tomography for brain tumors:
comparison of fluorodeoxyglucoseF18 and L-methyl-11C-methionine. AJNR Am J Neuroradiol 1996;17:345-53.
13. Lorbeboym M, Wallach F, Estok L, Mosesson RE, Sacher M, Kim CK
et al. Thallium-201 retention in focal intracranial lesions for differential diagnosis of primary lymphoma and nonmalignant lesions
in AIDS patients. J Nucl Med 1998;39:1366-9.
14. Hanson MW, Glantz MJ, Hoffman JM, Friedman AH, Burger PC,
Schold SC et al. FDG-PET in the selection of brain lesions for
biopsy. J Compux Assist Tomogr 1991;15:796-801.
15. Goldman S, Levivier M, Pirotte B, Brucher JM, Wikler D, Damhaut
P et al. Regional methionine and glucose uptake in high-grade
gliomas: a comparative study on PET-guided stereotactic biopsy.
J Nucl Med 1997;38:1459-62.
16. Hanson MW, Hoffman JM, Glantz MJ. FDG-PET in the early postoperative evaluation of patients with brain tumor. J Nucl Med
1990;31:799.
17. Di Chiro G, Oldfield E, Wright DC, De Michele D, Katz DA,
Patronas NJ et al. Cerebral necrosis after radiotherapy and/or
intraarterial chemotherapy for brain tumors: PET and neuropathologic studies. AJR Am J Radiol 1988;150:189-97.
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