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Fig-1. A and B: FLAIR and T2 post contrast MR Images demonstrate post-surgical changes related to the
left temporal craniotomy and mass resection. Ill defined, nodular enhancement is noted along the
margin of the resection cavity extending inferiorly into the left temporal lobe. Images courtesy of UCLA.
Fig-2. C, D, and E: Fused, PET and CT Images of 18F-FDOPA. Intense FDOPA uptake is noted in the left
temporal cortex lesion, which correlates with the MRI findings. This intense Uptake appears beyond the
enhancement demonstrated on MR images, compatible with the extension of the malignancy. Visually,
the FDOPA uptake is above the level of the contralateral striatum, with SUVmax 4.9. Physiologic FDOPA
uptake is also noted in the basal ganglia, and the thalami. Images courtesy of UCLA.
HPI: A 62-year-old right-handed male in his usual state of health, when he
suddenly awoke in his home, screaming, and in a state of confusion. The family
took him to the hospital where he had a grand mal seizure. Neuro-imaging revealed
a 3-cm enhancing left temporal lobe mass. Two weeks later, he underwent a left
temporal craniotomy and open biopsy of the mass. This revealed a glioblastoma
multiforme. Radiation therapy (60 gy) and temodar administration (130 mg po daily)
were completed. The patient continued to report mild word-finding difficulties and
mild cognitive slowness involving difficulties with memory, concentration, and
comprehension after surgery (for approximately 2 years). Physical examination
revealed a fluent speech without apparent paraphasias, but with mild subjective
word finding difficulties. The most recent Brain MRI and 18F-FDOPA scan are
shown.
Which of the following is the correct answer?
a) MRI is more sensitive than 18F-FDOPA to detect recurrent glioblastoma.
b) The SUV of 18F-FDOPA correlates with Ki-67 index of the brain tumor.
c) Dopaminergic pharmacological agents likely influence brain tumoral 18F-FDOPA
uptake.
Answer: b, The SUV of 18F-FDOPA correlates with Ki-67 proliferation index of
the brain tumor. Treatment of malignant brain lesions (primary and metastatic)
includes surgical resection, radiotherapy and/or chemotherapy. Radiation injury
is reported in up to 24% of patients treated with radiosurgery [Minniti G et al.
2010]. 1 Serial MRI studies are currently used for surveillance after radiation
therapy. The distinction between tumor recurrence, progression or radiation
injury is sometimes challenging. PET/CT with various radiotracers has been used
to assess recurrence. 18F-FDG PET was first used for imaging brain tumors
[Patronas et al. 1982 and Wong et al. 2002]. 2, 3
However, there are limitations mainly due to the high normal gray matter FDG uptake
affecting its sensitivity and limiting its use in low grade tumors. A few labeled amino
acid analogs have been introduced. 11C-methionine (11C-MET) was the first one. 11CMET has been studied for metastatic brain tumors, with reported sensitivities of 77.8
and 79%, and specificities of 100 and 75% [Terakava 2008].4 The use of
11C-MET
has been
limited due to the short physical half-life of 11C which limits its use to PET centers
with an on-site cyclotron. 18F-labeled amino acids (18F-FDOPA, and 18F-FET);
18F-labeled
nucleoside (18F-FLT) and 18F-FDOPA have also been introduced.
3,4-dihydroxy-6-18F-luoro-L-phenylalanine (18F-FDOPA) has been used for imaging
brain tumors, neuroendocrine tumors, and movement disorders for more than 20
years. Tumor tissue has a high uptake. This tracer provides favorable target-to
background ratios and improved image contrast. Tumor uptake of
18F-FDOPA
is
similar to that of 11C-MET. The distinction of brain tumor recurrence or progression
from radiation injury is possible with the use of 18F-FDOPA PET [Chen et al. 2006,
Lizaraga et al. 2014].5-7
Becherer et al. (2003) concluded that the diagnostic performances of
18F-FDOPA
11C-
11C-MET
and
are similar and 18F-FDOPA should be considered as an analogue to
MET for the evaluation of primary brain tumors and brain tumor recurrence.8
Chen et al. (2006), found false-negative results with 18F-FDG PET/CT while 18FFDOPA correctly differentiated recurrent low grade tumors from necrotic tissues. All
patients without active tumors showed no visible 18F-FDOPA uptake. They concluded
that 18F-FDOPA was superior to 18F-FDG in evaluating recurrent low grade brain
gliomas, which are difficult to assess with MRI.5
Schiepers et al. (2007) showed that tumoral time activity curves of 18F-FDOPA
are different than those from the striatum. Thus, dopaminergic metabolism or
pharmacological agents probably does not influence tumoral 18F-FDOPA
uptake.9
Gonzalez-Forero et al (2011) observed an excellent image contrast between the
lesions and the healthy brain tissue, while the SUV max value of malignant lesions was
greater than that of benign lesions.10
A sensitivity of 81.3% and a specificity of 84.3% have been recently reported for
18F-
of
FDOPA in the evaluation of brain malignancy [Lizaraga 2014].6 The sensitivity
18F-
FDOPA PET could be affected by lesion size, variability in amino acid
transport and proliferation rate. Similarly, its specificity could be altered by blood–
brain barrier breakdown, inflammation and other variables.
It has been observed that the intensity of 18F-FDOPA uptake by the metastatic brain
lesion might be used to predict its response to treatment with systemic
chemotherapy and/or radiotherapy [Harris 2012]. 6, 11
18F-FDOPA
PET SUVmax may more accurately identify regions of higher-grade in
patients with astrocytomas and will have utility in guiding stereotactic biopsy
selection. Using SUV-based thresholds to define high-grade portions of the tumor
may be valuable in delineating radiotherapy boost volumes.
It has been shown that 18F-FDOPA identifies high‐grade disease with higher accuracy
as compared to standard MRI (81% vs 38%), [Pafundi 2013]. 18F-FDOPA SUV
correlates with tumor grade as well as Ki-67 proliferation index in newly diagnosed
gliomas [Pafundi 2013].12
In conclusion: MRI provides anatomic information of lesions, which mostly reveals the
breakdown of the blood–brain barrier. Metabolic information provided by 18F- FDOPA
PET is useful in delineating the neoplastic component when a clarifying biopsy or
further therapy is indicated. Combining the higher spatial resolution of MRI with the
metabolic information provided by 18F-FDOPA, PET imaging could be useful to
evaluate suspicious areas for recurrence. Furthermore, 18F-FDOPA PET imaging
may have the potential to become an important parameter to improve the diagnostic
accuracy, prognosis prediction, surgical treatment planning and ultimately the
outcomes of patients with metastatic brain disease, although further investigation is
needed.
References:
1.
2.
Minniti G, Salvati M, Muni R, et al. Stereotactic radiosurgery plus whole-brain
radiotherapy for treatment of multiple metastases from non-small cell lung cancer.
Anticancer Res. Jul 2010;30(7):3055-3061.
Wong TZ, van der Westhuizen GJ, Coleman RE. Positron emission tomography imaging
of brain tumors. Neuroimaging Clin N Am. Nov 2002;12(4):615-626.
3.
Patronas NJ, Di Chiro G, Brooks RA, et al. Work in progress: [18F]
fluorodeoxyglucose and positron emission tomography in the evaluation of radiation
necrosis of the brain. Radiology. Sep 1982;144(4):885-889.
4.
Terakawa Y, Tsuyuguchi N, Iwai Y, et al. Diagnostic accuracy of 11C-methionine PET
for differentiation of recurrent brain tumors from radiation necrosis after radiotherapy. J
Nucl Med. May 2008;49(5):694-699.
5.
Chen W, Silverman DH, Delaloye S, et al. 18F-FDOPA PET imaging of brain tumors:
comparison study with 18F-FDG PET and evaluation of diagnostic accuracy. J Nucl
Med. Jun 2006;47(6):904-911.
6.
Lizarraga KJ, De Salles AA, Chen W. [18F] fluorodopa positron-emission
tomography: an emerging imaging modality for patients with brain metastases.
Expert Rev Med Devices. Jul 2014;11(4):327-329.
7.
Lizarraga KJ, Allen-Auerbach M, Czernin J, et al. 18F-FDOPA PET for
differentiating recurrent or progressive brain metastatic tumors from late or delayed
radiation injury after radiation treatment. J Nucl Med. Jan 2014;55(1):30-36.
8.
Becherer A, Karanikas G, Szabo M, et al. Brain tumour imaging with PET: a comparison
between [18F]fluorodopa and [11C]methionine. Eur J Nucl Med Mol Imaging. Nov
2003;30(11):1561-1567.
9.
Schiepers C, Chen W, Cloughesy T, Dahlbom M, Huang SC. 18F-FDOPA kinetics in
brain tumors. J Nucl Med. Oct 2007;48(10):1651-1661.
10.
Gonzalez-Forero M, Prieto E, Dominguez I, Vigil C, Penuelas I, Arbizu J. [Dual time
point 18F-FDOPA PET as a tool for characterizing brain tumors]. Rev Esp Med Nucl.
Mar-Apr 2011;30(2):88-93.
11.
Calabria F, Cascini GL. Current status of 18F-DOPA PET imaging in the
detection of brain tumor recurrence. Hell J Nucl Med. May-Aug
2015;18(2):152-156.
12.
Pafundi DH, Laack NN, Youland RS, et al. Biopsy validation of 18F-DOPA PET and
biodistribution in gliomas for neurosurgical planning and radiotherapy target
delineation: results of a prospective pilot study. Neuro Oncol. Aug 2013;15(8):10581067.