- Email: [email protected]
11C-Methionine uptake in secondary brain epilepsy
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ARTICLE IN PRESS Rev Esp Med Nucl Imagen Mol. 2014;xxx(xx):xxx–xxx
Clinical note 11
C-Methionine uptake in secondary brain epilepsy
E. Lopci a,∗ , L. Bello b , A. Chiti a a b
Nuclear Medicine, Humanitas Clinical and Research Center, Rozzano, MI, Italy Neurosurgery, Humanitas Clinical and Research Center, Rozzano, MI, Italy
a r t i c l e
i n f o
Article history: Received 27 November 2013 Accepted 16 December 2013 Available online xxx Keywords: 11 C-Methionine Positron Emission Tomography PET Epilepsy Seizure Brain metastasis
a b s t r a c t Carbon-11 methionine (11 C-Methionine) is a radio-labeled amino acid currently utilized in Positron Emission Tomography (PET) for imaging primary and metastatic brain tumors. Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of 11 C-Methionine in patients suffering from seizure; however, the tracer can find a proper utilization in this setting especially as a diagnostic complement to 18 F-Fluorodeoxyglucose (18 F-FDG). Herein we report the case of a 57-year-old patient presenting with epileptic crises secondary to a brain metastasis from bladder carcinoma, who was investigated in our institution with 11 C-Methionine PET. The scan documented the disease recurrence in the left parietal lobe associated with a diffused tracer uptake in the surrounding cerebral circumvolutions, derived from the comitial status. After surgical removal of the metastatic lesion, the patient experienced a complete recovery of symptoms and no further onset of secondary seizure. © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.
Captación de la 11 C-metionina en la epilepsia cerebral secundaria r e s u m e n Palabras clave: 11 C-metionina Tomografía por emisión de positrones PET Epilepsia Crisis convulsiva Metástasis cerebral
La 11 C-metionina es un aminoácido radiomarcado que se utiliza actualmente en la tomografía por emisión de positrones (PET) para obtener imágenes de tumores cerebrales primarios y metastáticos. Su aplicación clínica más extendida es la oncología, pero tiene el potencial de investigar otras situaciones no oncológicas. Hasta el momento existe una limitada evidencia del uso de 11 C-metionina en pacientes con crisis convulsiva; sin embargo, el radiotrazador puede tener utilidad en este campo especialmente como complemento diagnóstico de la 18 F-fluorodeoxiglucosa (18 F-FDG). Presentamos el caso de un paciente de 57 ˜ anos de edad con crisis epilépticas secundarias a metástasis cerebrales de un carcinoma de vejiga que fue explorado en nuestra Institución con 11 C-metionina PET. El estudio demostró la recidiva de la enfermedad en el lóbulo parietal izquierdo asociada con captación difusa en las circunvoluciones cerebrales de alrededor, derivada del status comicial. Después de la extirpación quirúrgica de la metástasis cerebral, el paciente experimentó una recuperación completa de los síntomas sin posterior inicio de crisis convulsivas secundarias. © 2013 Elsevier España, S.L. y SEMNIM. Todos los derechos reservados.
Introduction The broadest evidence regarding the use of Positron Emission Tomography (PET) imaging in patients affected by seizure relies on 18 F-Fluorodeoxyglucose (18 F-FDG).1–5 Typically the pattern of 18 F-FDG distribution is characterized by reduced metabolism (hypometabolic area) at the level of the epileptogenic tissue when the tracer is administered during the interictal phase, or vice versa there is an elevated tracer uptake (hypermetabolic area) in the involved area when there is a prompt injection during the comitial crisis. The site and the precise definition of the pathologic areas directly influence the treatment options,3 but despite the overall good sensitivity of 18 F-FDG PET, localization of epileptic foci is not always possible and requires in most cases the use
of additional software to overcome difficulties derived from pure visual analysis.2,5 Carbon-11 methionine (11 C-Methionine) is a radio-labeled amino acid currently utilized in PET for imaging primary and metastatic brain tumors.6 Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of 11 C-Methionine in patients suffering from seizure, however the tracer can find a proper utilization in this setting especially as a diagnostic complement to 18 F-Fluorodeoxyglucose (18 F-FDG).7–10 We present the clinical case of a patient affected by brain metastasis associated with secondary seizure, which was correctly identified on 11 C-Methionine PET. Case report
∗ Corresponding author. E-mail addresses: [email protected], [email protected] (E. Lopci).
The clinical case presented herein regards a 57-year-old female affected by a cerebral recurrence of bladder carcinoma localized
2253-654X/$ – see front matter © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved. http://dx.doi.org/10.1016/j.remn.2013.12.008
Please cite this article in press as: Lopci E, et al. 11 C-Methionine uptake in secondary brain epilepsy. Rev Esp Med Nucl Imagen Mol. 2014. http://dx.doi.org/10.1016/j.remn.2013.12.008
G Model REMNIM-581; No. of Pages 3
ARTICLE IN PRESS E. Lopci et al. / Rev Esp Med Nucl Imagen Mol. 2014;xxx(xx):xxx–xxx
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b
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d
e
f
g
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Fig. 1. Transaxial sections of the cerebral ceCT of the patient (a)–(d) and corresponding fused images of 11 C-Methionine PET/CT (e)–(h). The site of recurrent brain metastasis is clearly visible in the left rolandic region, thanks to the increased contrast enhancement present in the peripheral territories of the ablative cavity, and in the same sites PET scanning demonstrates a highly increased 11 C-Methionine uptake (arrowheads). In addition to this malignant lesion, on PET scan there is an abnormal tracer uptake in the surrounding cerebral convolutions (yellow and red arrows), interesting the motor-sensitive areas, and interpreted as functional alteration secondary to the epileptic feature.
in the left parietal lobe. The patient had already been treated with radio-ablation in March 2010, but 7 months later had experienced three generalized epileptic crises and had started complaining right-handed motor-sensitive deficit. The first therapeutic decision was to start anti-epileptic treatment with levetiracetam, in association with mannitol as antiedematous pharmaceutical support. After an apparent remission of clinical symptoms, 4 months later the patient had other two partial motor crises, which addressed her to our institution for the necessary instrumental investigations. On that occasion the patient underwent cerebral contrastenhanced CT (ceCT), according to standard procedure, and 11 C-Methionine PET, in order to define disease status. For the PET scan she received 328 MBq (4.6 mCi/kg) of tracer and images were acquired 10 min later with a Siemens Biograph 6 LSO (10 min emission for 1 bed position, 256 × 256 matrix, zoom 2.0 and OSEM iterative algorithm; 80 mAs, 130 kV and 5 mm collimation 6 mm × 3 mm for the localization CT). Instrumental data derived from both imaging modalities confirmed the presence of malignant tissue in the peripheral territories of the post-ablative cavity (rolandic region): the lesion presented as a contrast-enhanced area on CT and was characterized by a highly increased 11 C-Methionine uptake on PET (Fig. 1: arrowheads). In addition to the malignant findings, the PET scan demonstrated some abnormal tracer uptake moderately diffused in the frontoparietal lobes, broadly outside the margins of the tumor site, interesting almost exclusively the cerebral circumvolutions (Fig. 1: arrows). This additional pattern was interpreted as a functional alteration related to the underlying comitial status. The patient was consequently addressed to a selective surgical removal of the malignant lesion in the left rolandic region, which resulted in a complete remission of the epileptic crises.
pattern in the distribution of the two radiopharmaceuticals in the epileptic focus during the interictal phase, typically characterized by hypometabolism on 18 F-FDG PET with on counterpart an increased uptake on 11 C-Methionine PET. Something similar has been reported also in two other case reports, both investigating intractable seizure in children.7,9 More recently, also Phi et al.10 have thoroughly investigated the role of 11 C-Methionine in epileptic children when trying to differentiate FCD from neural and glial tumors as underlying etiopathology. Their findings documented a different uptake pattern for malignant lesions and FCD, with the later one associated to hypometabolism on 18 F-FDG PET and mild-hypo to normal uptake on 11 C-Methionine PET. In our patient the underlying cause for seizure appears to be the tumor recurrence, whereas the epileptic alteration is documented as a mildly diffused uptake of 11 C-Methionine in the cortical areas involved by the secondary seizure manifesting with functional deficit and motor crises. This setting is quite new and to our knowledge this is the first report of its kind in adults. Undoubtedly age and clinical setting must have somehow influenced differences in imaging findings and outcome data; anyhow our case study and all previous reports similarly suggest the potential benefit and application of 11 C-Methionie PET in epileptic patients. This would be particularly relevant when selective ablation is advised and a precise contouring of the area involved in seizure must be given prior to surgery. Further studies are therefore welcome in order to investigate the role of 11 C-Methionine PET in this setting and assess its proper application in the management of patients affected by seizure.
References Discussion The first report documenting the use of 11 C-Methionine in epileptic patients belongs to Madakasira et al.,8 who in 2002 described the utility of the dual-tracer imaging (18 F-FDG and 11 C-Methionine) in the same child affected by focal cortical dysplasia (FCD). In their report the authors describe a complementary
1. Struck AF, Hall LT, Floberg JM, Perlman SB, Dulli DA. Surgical decision making in temporal lobe epilepsy: A comparison of [(18)F]FDG-PET, MRI, and EEG. Epilepsy Behav. 2011;22:293–7. 2. Sperling MR, Alavi A, Reivich M, French JA, O’Connor MJ. False lateralization of temporal lobe epilepsy with FDG positron emission tomography. Epilepsia. 1995;36:722–7. 3. Fish DR, Smith SJ, Quesney LF, Andermann F, Rasmussen T. Surgical treatment of children with medically intractable frontal or temporal lobe epilepsy: results and highlights of 40 years’ experience. Epilepsia. 1993;34:244–7.
Please cite this article in press as: Lopci E, et al. 11 C-Methionine uptake in secondary brain epilepsy. Rev Esp Med Nucl Imagen Mol. 2014. http://dx.doi.org/10.1016/j.remn.2013.12.008
G Model REMNIM-581; No. of Pages 3
ARTICLE IN PRESS E. Lopci et al. / Rev Esp Med Nucl Imagen Mol. 2014;xxx(xx):xxx–xxx
4. Lee JS, Lee DS, Kim SK, Lee SK, Chung JK, Lee MC, et al. Localization of epileptogenic zones in F-18 FDG brain PET of patients with temporal lobe epilepsy using artificial neural network. IEEE Trans Med Imaging. 2000;19:347–55. 5. Wong CY, Geller EB, Chen EQ, Macintyre WJ, Morris 3rd HH, Raja S, et al. Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging. J Nucl Med. 1996;37:1094–100. 6. Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42:432–45. 7. Metsahonkala L, Aarimaa T, Sonninen P, Mikola H, Ruotsalainen U, Bergman JCT. MRI, and PET in a case of intractable epilepsy. Child’s Nerv Syst. 1996;12:421–4.
3
8. Madakasira PV, Simkins R, Narayanan T, Dunigan K, Poelstra RJ, Mantil J. Cortical dysplasia localized by [11C]Methionine positron emission tomography: case report. Am J Neuroradiol. 2002;23:844–6. 9. Kocher L, Rambaud L, Rousselle C, Mottolese C, Ryvlin P, Gonnaud PM. Painful seizures with allodynia in an 11-year-old boy. Dev Med Child Neurol. 1999;41:704–7. 10. Phi JH, Paeng JC, Lee HS, Wang KC, Cho BK, Lee JY, et al. Evaluation of focal cortical dysplasia and mixed neuronal and glial tumors in pediatric epilepsy patients using 18F-FDG and 11C-Methionine PET. J Nucl Med. 2010;51: 728–34.
Please cite this article in press as: Lopci E, et al. 11 C-Methionine uptake in secondary brain epilepsy. Rev Esp Med Nucl Imagen Mol. 2014. http://dx.doi.org/10.1016/j.remn.2013.12.008
ARTICLE IN PRESS Rev Esp Med Nucl Imagen Mol. 2014;xxx(xx):xxx–xxx
Clinical note 11
C-Methionine uptake in secondary brain epilepsy
E. Lopci a,∗ , L. Bello b , A. Chiti a a b
Nuclear Medicine, Humanitas Clinical and Research Center, Rozzano, MI, Italy Neurosurgery, Humanitas Clinical and Research Center, Rozzano, MI, Italy
a r t i c l e
i n f o
Article history: Received 27 November 2013 Accepted 16 December 2013 Available online xxx Keywords: 11 C-Methionine Positron Emission Tomography PET Epilepsy Seizure Brain metastasis
a b s t r a c t Carbon-11 methionine (11 C-Methionine) is a radio-labeled amino acid currently utilized in Positron Emission Tomography (PET) for imaging primary and metastatic brain tumors. Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of 11 C-Methionine in patients suffering from seizure; however, the tracer can find a proper utilization in this setting especially as a diagnostic complement to 18 F-Fluorodeoxyglucose (18 F-FDG). Herein we report the case of a 57-year-old patient presenting with epileptic crises secondary to a brain metastasis from bladder carcinoma, who was investigated in our institution with 11 C-Methionine PET. The scan documented the disease recurrence in the left parietal lobe associated with a diffused tracer uptake in the surrounding cerebral circumvolutions, derived from the comitial status. After surgical removal of the metastatic lesion, the patient experienced a complete recovery of symptoms and no further onset of secondary seizure. © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.
Captación de la 11 C-metionina en la epilepsia cerebral secundaria r e s u m e n Palabras clave: 11 C-metionina Tomografía por emisión de positrones PET Epilepsia Crisis convulsiva Metástasis cerebral
La 11 C-metionina es un aminoácido radiomarcado que se utiliza actualmente en la tomografía por emisión de positrones (PET) para obtener imágenes de tumores cerebrales primarios y metastáticos. Su aplicación clínica más extendida es la oncología, pero tiene el potencial de investigar otras situaciones no oncológicas. Hasta el momento existe una limitada evidencia del uso de 11 C-metionina en pacientes con crisis convulsiva; sin embargo, el radiotrazador puede tener utilidad en este campo especialmente como complemento diagnóstico de la 18 F-fluorodeoxiglucosa (18 F-FDG). Presentamos el caso de un paciente de 57 ˜ anos de edad con crisis epilépticas secundarias a metástasis cerebrales de un carcinoma de vejiga que fue explorado en nuestra Institución con 11 C-metionina PET. El estudio demostró la recidiva de la enfermedad en el lóbulo parietal izquierdo asociada con captación difusa en las circunvoluciones cerebrales de alrededor, derivada del status comicial. Después de la extirpación quirúrgica de la metástasis cerebral, el paciente experimentó una recuperación completa de los síntomas sin posterior inicio de crisis convulsivas secundarias. © 2013 Elsevier España, S.L. y SEMNIM. Todos los derechos reservados.
Introduction The broadest evidence regarding the use of Positron Emission Tomography (PET) imaging in patients affected by seizure relies on 18 F-Fluorodeoxyglucose (18 F-FDG).1–5 Typically the pattern of 18 F-FDG distribution is characterized by reduced metabolism (hypometabolic area) at the level of the epileptogenic tissue when the tracer is administered during the interictal phase, or vice versa there is an elevated tracer uptake (hypermetabolic area) in the involved area when there is a prompt injection during the comitial crisis. The site and the precise definition of the pathologic areas directly influence the treatment options,3 but despite the overall good sensitivity of 18 F-FDG PET, localization of epileptic foci is not always possible and requires in most cases the use
of additional software to overcome difficulties derived from pure visual analysis.2,5 Carbon-11 methionine (11 C-Methionine) is a radio-labeled amino acid currently utilized in PET for imaging primary and metastatic brain tumors.6 Its clinical use relies mostly on oncologic applications, but the tracer has the potential to investigate other non-malignant conditions. So far, very limited evidence concerns the use of 11 C-Methionine in patients suffering from seizure, however the tracer can find a proper utilization in this setting especially as a diagnostic complement to 18 F-Fluorodeoxyglucose (18 F-FDG).7–10 We present the clinical case of a patient affected by brain metastasis associated with secondary seizure, which was correctly identified on 11 C-Methionine PET. Case report
∗ Corresponding author. E-mail addresses: [email protected], [email protected] (E. Lopci).
The clinical case presented herein regards a 57-year-old female affected by a cerebral recurrence of bladder carcinoma localized
2253-654X/$ – see front matter © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved. http://dx.doi.org/10.1016/j.remn.2013.12.008
Please cite this article in press as: Lopci E, et al. 11 C-Methionine uptake in secondary brain epilepsy. Rev Esp Med Nucl Imagen Mol. 2014. http://dx.doi.org/10.1016/j.remn.2013.12.008
G Model REMNIM-581; No. of Pages 3
ARTICLE IN PRESS E. Lopci et al. / Rev Esp Med Nucl Imagen Mol. 2014;xxx(xx):xxx–xxx
2
a
b
c
d
e
f
g
h
Fig. 1. Transaxial sections of the cerebral ceCT of the patient (a)–(d) and corresponding fused images of 11 C-Methionine PET/CT (e)–(h). The site of recurrent brain metastasis is clearly visible in the left rolandic region, thanks to the increased contrast enhancement present in the peripheral territories of the ablative cavity, and in the same sites PET scanning demonstrates a highly increased 11 C-Methionine uptake (arrowheads). In addition to this malignant lesion, on PET scan there is an abnormal tracer uptake in the surrounding cerebral convolutions (yellow and red arrows), interesting the motor-sensitive areas, and interpreted as functional alteration secondary to the epileptic feature.
in the left parietal lobe. The patient had already been treated with radio-ablation in March 2010, but 7 months later had experienced three generalized epileptic crises and had started complaining right-handed motor-sensitive deficit. The first therapeutic decision was to start anti-epileptic treatment with levetiracetam, in association with mannitol as antiedematous pharmaceutical support. After an apparent remission of clinical symptoms, 4 months later the patient had other two partial motor crises, which addressed her to our institution for the necessary instrumental investigations. On that occasion the patient underwent cerebral contrastenhanced CT (ceCT), according to standard procedure, and 11 C-Methionine PET, in order to define disease status. For the PET scan she received 328 MBq (4.6 mCi/kg) of tracer and images were acquired 10 min later with a Siemens Biograph 6 LSO (10 min emission for 1 bed position, 256 × 256 matrix, zoom 2.0 and OSEM iterative algorithm; 80 mAs, 130 kV and 5 mm collimation 6 mm × 3 mm for the localization CT). Instrumental data derived from both imaging modalities confirmed the presence of malignant tissue in the peripheral territories of the post-ablative cavity (rolandic region): the lesion presented as a contrast-enhanced area on CT and was characterized by a highly increased 11 C-Methionine uptake on PET (Fig. 1: arrowheads). In addition to the malignant findings, the PET scan demonstrated some abnormal tracer uptake moderately diffused in the frontoparietal lobes, broadly outside the margins of the tumor site, interesting almost exclusively the cerebral circumvolutions (Fig. 1: arrows). This additional pattern was interpreted as a functional alteration related to the underlying comitial status. The patient was consequently addressed to a selective surgical removal of the malignant lesion in the left rolandic region, which resulted in a complete remission of the epileptic crises.
pattern in the distribution of the two radiopharmaceuticals in the epileptic focus during the interictal phase, typically characterized by hypometabolism on 18 F-FDG PET with on counterpart an increased uptake on 11 C-Methionine PET. Something similar has been reported also in two other case reports, both investigating intractable seizure in children.7,9 More recently, also Phi et al.10 have thoroughly investigated the role of 11 C-Methionine in epileptic children when trying to differentiate FCD from neural and glial tumors as underlying etiopathology. Their findings documented a different uptake pattern for malignant lesions and FCD, with the later one associated to hypometabolism on 18 F-FDG PET and mild-hypo to normal uptake on 11 C-Methionine PET. In our patient the underlying cause for seizure appears to be the tumor recurrence, whereas the epileptic alteration is documented as a mildly diffused uptake of 11 C-Methionine in the cortical areas involved by the secondary seizure manifesting with functional deficit and motor crises. This setting is quite new and to our knowledge this is the first report of its kind in adults. Undoubtedly age and clinical setting must have somehow influenced differences in imaging findings and outcome data; anyhow our case study and all previous reports similarly suggest the potential benefit and application of 11 C-Methionie PET in epileptic patients. This would be particularly relevant when selective ablation is advised and a precise contouring of the area involved in seizure must be given prior to surgery. Further studies are therefore welcome in order to investigate the role of 11 C-Methionine PET in this setting and assess its proper application in the management of patients affected by seizure.
References Discussion The first report documenting the use of 11 C-Methionine in epileptic patients belongs to Madakasira et al.,8 who in 2002 described the utility of the dual-tracer imaging (18 F-FDG and 11 C-Methionine) in the same child affected by focal cortical dysplasia (FCD). In their report the authors describe a complementary
1. Struck AF, Hall LT, Floberg JM, Perlman SB, Dulli DA. Surgical decision making in temporal lobe epilepsy: A comparison of [(18)F]FDG-PET, MRI, and EEG. Epilepsy Behav. 2011;22:293–7. 2. Sperling MR, Alavi A, Reivich M, French JA, O’Connor MJ. False lateralization of temporal lobe epilepsy with FDG positron emission tomography. Epilepsia. 1995;36:722–7. 3. Fish DR, Smith SJ, Quesney LF, Andermann F, Rasmussen T. Surgical treatment of children with medically intractable frontal or temporal lobe epilepsy: results and highlights of 40 years’ experience. Epilepsia. 1993;34:244–7.
Please cite this article in press as: Lopci E, et al. 11 C-Methionine uptake in secondary brain epilepsy. Rev Esp Med Nucl Imagen Mol. 2014. http://dx.doi.org/10.1016/j.remn.2013.12.008
G Model REMNIM-581; No. of Pages 3
ARTICLE IN PRESS E. Lopci et al. / Rev Esp Med Nucl Imagen Mol. 2014;xxx(xx):xxx–xxx
4. Lee JS, Lee DS, Kim SK, Lee SK, Chung JK, Lee MC, et al. Localization of epileptogenic zones in F-18 FDG brain PET of patients with temporal lobe epilepsy using artificial neural network. IEEE Trans Med Imaging. 2000;19:347–55. 5. Wong CY, Geller EB, Chen EQ, Macintyre WJ, Morris 3rd HH, Raja S, et al. Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging. J Nucl Med. 1996;37:1094–100. 6. Jager PL, Vaalburg W, Pruim J, de Vries EG, Langen KJ, Piers DA. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42:432–45. 7. Metsahonkala L, Aarimaa T, Sonninen P, Mikola H, Ruotsalainen U, Bergman JCT. MRI, and PET in a case of intractable epilepsy. Child’s Nerv Syst. 1996;12:421–4.
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8. Madakasira PV, Simkins R, Narayanan T, Dunigan K, Poelstra RJ, Mantil J. Cortical dysplasia localized by [11C]Methionine positron emission tomography: case report. Am J Neuroradiol. 2002;23:844–6. 9. Kocher L, Rambaud L, Rousselle C, Mottolese C, Ryvlin P, Gonnaud PM. Painful seizures with allodynia in an 11-year-old boy. Dev Med Child Neurol. 1999;41:704–7. 10. Phi JH, Paeng JC, Lee HS, Wang KC, Cho BK, Lee JY, et al. Evaluation of focal cortical dysplasia and mixed neuronal and glial tumors in pediatric epilepsy patients using 18F-FDG and 11C-Methionine PET. J Nucl Med. 2010;51: 728–34.
Please cite this article in press as: Lopci E, et al. 11 C-Methionine uptake in secondary brain epilepsy. Rev Esp Med Nucl Imagen Mol. 2014. http://dx.doi.org/10.1016/j.remn.2013.12.008