11C-L-methionine positron emission tomography in the clinical management of cerebral gliomas.

Positron emission tomography (PET) using L-[methyl-(11)C]-methionine (MET) is the most popular amino acid imaging modality in oncology, although its use is restricted to PET centers with an in-house cyclotron facility. This review focuses on the role of MET-PET in imaging of cerebral gliomas. The biological background of tumor imaging with methionine is discussed with particular emphasis on cellular amino acid transport, amino acid utilization in brain, normal metabolism of methionine, and its alterations in cancer. The role of MET-PET in clinical management of cerebral gliomas in initial diagnosis, differentiation of tumor recurrence from radiation injury, grading, prognostication, tumor-extent delineation, biopsy planning, surgical resection and radiotherapy planning, and assessment of response to therapy is also reviewed in detail.

Increased F-18 FDG uptake on positron emission tomography/computed tomography imaging caused by plantar fibromatosis.

We detail the history and evaluation of a 68-year-old man who had head-to-toe PET/CT scanning that showed a focal area of increased FDG uptake in the left medial foot. This was thought to be recurrence of his melanoma. The patient was asymptomatic. He had a history of malignant melanoma of the right ear, which was removed in 2001. On biopsy, the foot lesion was diagnosed as plantar fibromatosis. Plantar fibromatosis is a benign fibroblastic condition, which can be indistinguishable from malignancy in head-to-toe PET/CT scans. Awareness of their potential appearance on PET and PET/CT will aid in the appropriate staging of oncology patients.

D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia.

BACKGROUND: Abnormalities in the dopaminergic system are implicated in schizophrenia. [F-18]fallypride is a highly selective, high affinity PET ligand well suited for measuring D2/D3 receptor availability in the extrastriatal regions of the brain including thalamus, prefrontal, cingulate, and temporal cortex, brain regions implicated in schizophrenia with other imaging modalities. METHODS: Resting [F-18]fallypride PET studies were acquired together with anatomical MRI for accurate coregistration and image analysis on 15 drug naïve schizophrenics (10 men, 5 women, mean age 28.5 years) and 15 matched controls (9 men, 6 women, mean age 27.4 years). Dopamine D2/D3 receptor levels were measured as binding potential (BP). The fallypride BP images of each subject were spatially normalized and subsequently smoothed for group comparison. Measures of significance between the schizophrenic and control groups were determined using statistical parametric mapping (SPM). The medial dorsal nucleus and pulvinar were also traced on coregistered MRI for detailed assessment of BP in these regions. RESULTS: The thalamus of patients with schizophrenia had lower [F-18]fallypride BP than normal controls and this was the brain area with the greatest difference (range -8.5% to -27.2%). Left medial dorsal nucleus and left pulvinar showed the greatest decreases (-21.6% and -27.2% respectively). The patients with schizophrenia also demonstrated D2/D3 BP reduction in the amygdala region, cingulate gyrus, and the temporal cortices. CONCLUSIONS: These findings suggest that drug naïve patients with schizophrenia have significant reductions in extrastratial D2/D3 receptor availability. The reductions were most prominent in regions of the thalamus, replicating other studies both with high affinity D2/D3 ligands and consistent with FDG-PET studies, further supporting the hypothesis of thalamic abnormalities in this patient population.

Abdominal positron-emission tomography lesions with increased standardized uptake values correlate with intraoperative findings.

BACKGROUND: The reporting of standardized uptake value (SUV) on fluoro-2-deoxy-D-glucose positron-emission tomography (FDG-PET) in colorectal cancer is becoming common practice, but its clinical utility remains to be determined. This study was designed to compare FDG-PET uptake as measured by SUV with operative findings. METHODS: A colorectal cancer database was queried to identify patients who underwent FDG-PET scans with reported SUVs followed by exploratory laparotomy within 3 months and compare these results to determine FDG-PET sensitivity. RESULTS: Of 46 patients, 16 (34.8%) were found to be have increased extent of disease intraoperatively than seen on FDG-PET scan. This patient population had a statistically significant decreased mean maximal SUV than the patients whose FDG-PET scan equaled intraoperative findings (P < .025). CONCLUSIONS: This initial study indicates patients with potentially resectable disease by PET scan but decreased FDG uptake should undergo laparoscopic evaluation before performing laparotomy.

Combined C-11 methionine and F-18 FDG PET imaging in a case of neurosarcoidosis.

PURPOSE: PET scanning of the brain with F-18 FDG and C-11 methionine (MET) is useful for characterizing brain lesions discovered at MRI or CT. Most positive PET scans indicate malignancy. However, this case report demonstrates positive F-18 FDG and C-11 MET PET scans in a patient with a nonmalignant condition, neurosarcoidosis. MATERIALS AND METHODS: We detail the history and evaluation of a 59-year-old woman who presented with ataxia. The patient's evaluation included a contrast-enhanced MRI followed by PET scanning of the brain with C-11 MET and of the brain and trunk with F-18 FDG. The patient subsequently underwent biopsy of a lesion as directed by MRI and PET. RESULTS: The MRI demonstrated multiple enhancing leptomeningeal lesions consistent with metastatic disease. PET with F-18 FDG and C-11 MET demonstrated lesions in both cerebellar hemispheres with F-18 FDG accumulation in the mediastinum and left hilum. Biopsy of a brain lesion directed by MRI and PET revealed sarcoidosis. CONCLUSIONS: In evaluating brain lesions, PET with F-18 FDG and C-11 MET can help localize the lesion best suited for biopsy. However, not all lesions that have increased uptake on C-11 MET or F-18 FDG PET are malignant. Granulomatous inflammatory diseases such as neurosarcoidosis should also be considered in the differential diagnosis.

Gallbladder metastasis from malignant melanoma: diagnosis with FDG PET/CT.

Melanoma with metastasis to the gallbladder is sometimes seen on autopsy but is rarely seen in living patients, in part because it is often asymptomatic. A 67-year-old man with a history of malignant melanoma in situ underwent an F-18 FDG PET/CT scan, which showed a gallbladder focus (SUV 16.9). Four months later, on the repeat FDG PET/CT scan, a new lesion in the gallbladder was noted. Laparoscopic cholecystectomy was done and histopathologic findings were consistent with gallbladder metastasis of melanoma. PET/CT detects metastasis at unusual sites accurately and is helpful in correct staging and management of patients with melanoma.

Thalamic and prefrontal FDG uptake in never medicated patients with schizophrenia.

OBJECTIVE: Because neuroleptic treatment may cause long-lasting changes in brain structure and function, a group of patients with schizophrenia who had never been medicated was recruited to examine regional glucose metabolic rates in the frontal-striato-thalamic circuit. METHOD: Twelve never medicated patients with schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers (eight men and five women; mean age=28.5 years) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography, and coregistered anatomical magnetic resonance imaging scans were also obtained. During FDG uptake, subjects performed a spatial attention task previously shown to activate the pulvinar region of the thalamus. RESULTS: Diminished regional glucose metabolism was found in the medial dorsal nucleus, posterior thalamus, and prefrontal cortex of patients with schizophrenia relative to normal volunteers, extending earlier results from studies of medicated and previously medicated patients. CONCLUSIONS: The finding of lower relative metabolic rates in the frontothalamic circuits of patients with schizophrenia is consistent with extended circuit deficits involving interactions of frontal executive areas with thalamic sensory and association processes.

High 2-deoxy-2[F-18]fluoro-D-glucose uptake on positron emission tomography in hibernoma originally thought to be myxoid liposarcoma.

PURPOSE: The purpose of the study is to describe the rare tumor on 2-deoxy-2[F-18]fluoro-D-glucose (FDG) positron emission tomography (PET). PROCEDURE: A 33-year-old male was diagnosed with high uptake lesion on FDG-PET scanning, which was found to be hibernoma on excision. RESULTS: Hibernoma, originally confused with liposarcoma based on its PET and computed tomography presentation, was excised and correctly identified by pathology. CONCLUSION: Although found to be benign, radiological and FDG-PET scanning results were indistinguishable from malignancy, and biopsy is required to exclude neoplasm.

Measuring the in vivo binding parameters of [18F]-fallypride in monkeys using a PET multiple-injection protocol.

The goal of this work was to quantify the in vivo transport and binding parameters of [F-18]fallypride and the D2/D3 receptor density (B'max) in both the striatal (putamen, caudate, ventral striatum) and extrastriatal regions (thalamus, amygdala, cerebellum, temporal and frontal cortices) of the rhesus monkey brain. Multiple-injection PET experimental protocols with injections of radiolabeled and unlabeled doses of fallypride were used to estimate the K1, k2, kon/VR, koff and B'max kinetic parameters. The experimental design was chosen using the D-optimal criterion to maximize the precision of the estimated binding parameters for the various brain regions. There was a significant range in B'max for the putamen (27 pmol/mL), caudate (23 pmol/mL), ventral striatum (14 pmol/mL), thalamus (1.8 pmol/mL) and amygdala (0.9 pmol/mL). Significant receptor binding was also found in the cortical regions. Knowledge of these in vivo rate constants serves as a necessary step in using [F-18]fallypride PET to measure D2/D3 receptor density and drug occupancy in clinical research applications. We believe the precise parameter estimates derived from these complicated experimental protocols are necessary for proper application of drug occupancy and clinical research studies with [F-18]fallypride, which often rely on the validity of assumptions regarding the model parameters.

Functional imaging in Lhermitte-Duclose disease.

PURPOSE: A comprehensive metabolic characterization of a patient with dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos Disease (LDD) is presented. PROCEDURES: Assessment using 2-deoxy-2-[18F]fluoro-D-glucose (FDG), carbon-11-labeled methionine (11C-MET), carbon-11-labeled choline (11C-Choline) positron emission tomography (PET), and 1H-proton magnetic resonance spectroscopy (MRS) was carried out in a 30-year-old Caucasian woman. RESULTS: FDG-PET revealed hypermetabolism of the tumor. 11C-MET-PET revealed moderate uptake and 11C-Choline showed no uptake. 1H-MRS demonstrated an elevated level of lactate and decreased levels of choline (Cho) and myoinositol. CONCLUSION: Functional imaging in LDD reflects the dual pathological features of neoplasm and hamartoma.

A comparative study on the uptake and incorporation of radiolabeled methionine, choline and fluorodeoxyglucose in human astrocytoma.

PURPOSE: The goal of this investigation was to evaluate uptake and incorporation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG), 11C-methionine, and 11C-choline in 17 patients suspected of grade-II and grade-III tumors using positron emission tomography (PET) and use in vitro astrocytoma cell lines in order to support in vivo findings. METHODS: Seventeen patients with suspected astrocytomas (9 grade-II and 8 grade-III) were studied by PET with FDG and 11C-methionine; and one patient (grade-III) with FDG, 11C-methionine and 11C-choline. Uptake of PET molecular imaging probe was quantitative based on tumor to corresponding contralateral-region uptake ratio, tumor to mean-cortical-uptake ratio, and tumor to white matter uptake ratio. This was correlated with World Health Organization histology grading system and clinical follow-up. Uptake and incorporation of 3H-methionine, 3H-choline and FDG into lipid, RNA, DNA, and protein were investigated in a grade-III human tumor brain-14 astrocytoma cell line. RESULTS: A time-dependent increase in the total uptake of 3H-methionine, 3H-choline and FDG was observed in human tumor brain-14 astrocytoma-III cell line. 3H-methionine was incorporated predominantly into proteins (in excess of 40% at 1 h) while 3H-choline incorporated primarily into lipids (in excess of 60% at 1 hr). Total uptake of FDG was accounted for in the free-pool supernatant fraction. In all patients, PET images of 11C-methionine and FDG provided higher tumor to white matter ratios than tumor to corresponding contra-lateral region ratios and tumor to mean cortical uptake ratios. In grade II patients, FDG did not exhibit significant increase in tumor uptake, while 11C-methionine was a good predictor with ratios of approximately 1.50 +/- 0.48. In grade III patients, both FDG and 11C-methionine exhibited higher ratios than for grade II, with 11C-methionine being the greatest (ratios of 2.50 +/- 0.85), possibly suggesting enhanced protein synthesis. With respect to tumor delineating potential, 11C-choline may be equal to or slightly better than 11C-methionine in the subject evaluated with all three probes. CONCLUSIONS: Results suggest that a combination of FDG and 11C-methionine is useful in the prediction of histological grade of astrocytomas. In addition, 11C-methionine is better than FDG in delineating tumor boundary for low-grade gliomas. In vitro results suggest that 3H-methionine is significantly incorporated into proteins and provides the major driving force in the uptake of 11C-methionine observed in PET images.

Cortical dysplasia localized by [11C]methionine positron emission tomography: case report.

Numerous functional neuroimaging techniques have progressively been added to the presurgical evaluation of refractory partial epilepsies. These investigations can help confirm the origin of seizure onset previously suggested by MR imaging and electro-clinical data, provide independent prognostic information, and provide critical diagnostic value when MR imaging results are strictly normal or show multifocal abnormalities. Of the various functional neuroimaging modalities, [11C]methionine positron emission tomography for methionine uptake into seizure foci is still in the preliminary stages of investigation. A single case of medically intractable epilepsy with focal cortical dysplasia documented by [11C]methionine positron emission tomography and possible hypotheses to explain the methionine uptake into the seizure focus are described below.

Clinical utility of 11C-flumazenil positron emission tomography in intractable temporal lobe epilepsy.

BACKGROUND: 11C-flumazenil (FMZ) positron emission tomography (PET) is a new entrant into the armamentarium for pre-surgical evaluation of patients with intractable temporal lobe epilepsy (TLE). AIMS: To analyze the clinical utility of FMZ PET to detect lesional and remote cortical areas of abnormal benzodiazepine receptor binding in relation to magnetic resonance imaging (MRI), 2-Deoxy-2 [18F] fluoro-D-glucose, (18F FDG) PET, electrophysiological findings and semiology of epilepsy in patients with intractable TLE. MATERIALS AND METHODS: Patients underwent a high resolution MRI, prolonged Video-EEG monitoring before 18F FDG and 11C FMZ PET studies. Regional cortical FMZ PET abnormalities were defined on co-registered PET images using an objective method based on definition of areas of abnormal asymmetry (asymmetry index {AI}>10%). SETTINGS AND DESIGN: Prospective. STATISTICAL ANALYSIS: Student's "t" test. RESULTS: Twenty patients (Mean age: 35.2 years [20-51]; M:F=12:8) completed the study. Mean age at seizure onset was 10.3 years (birth-38 years); mean duration, 23.9 years (6-50 years). Concordance with the MRI lesion was seen in 10 patients (nine with hippocampal sclerosis and one with tuberous sclerosis). In the other 10, with either normal or ambiguous MRI findings, FMZ and FDG uptake were abnormal in all, concordant with the electrophysiological localization of the epileptic foci. Remote FMZ PET abnormalities (n=18) were associated with early age of seizure onset (P=0.005) and long duration of epilepsy (P=0.01). CONCLUSIONS: FMZ-binding asymmetry is a sensitive method to detect regions of epileptic foci in patients with intractable TLE.

Radiation dose to the fetus from [(18)F]-FDG administration during the second trimester of pregnancy.

The authors estimated the fetal radiation dose from [(18)F]-FDG in a rare case of a woman who underwent a PET/CT scan during the second trimester of pregnancy. The patient, a 27-y-old female with a paraganglioma, received 181.3 MBq [(18)F]-FDG. From the concentrations of radioactivity measured on the images, the time-integrated activity coefficients of the fetus and the placenta were derived. The time-integrated activity coefficients of the mother's organs were taken from the standard values of ICRP publication 106. The final fetal dose was calculated using the 6-mo pregnant model of the OLINDA/EXM software. The fetus showed an overall low and homogeneous [(18)F]-FDG uptake, with an average concentration of 2.41 kBq cm(-3). The uptake in the placenta was generally higher (average concentration = 3.69 kBq cm(-3)). The estimated time-integrated activity coefficients were 0.0130 and 0.0058 Bq h Bq(-1) for the fetus and the placenta, respectively. The final average dose to the fetus was 1.97 × 10(-2) mGy MBq(-1) (3.6 mGy in this patient who received 181.3 MBq). Therefore, the dose to the fetus from [(18)F]-FDG administration during the second trimester of pregnancy is low. When medically indicated, pregnancy should not be a categorical basis for withholding [(18)F]-FDG PET scans.

11C-methionine PET for grading and prognostication in gliomas: a comparison study with 18F-FDG PET and contrast enhancement on MRI.

UNLABELLED: The aim of this study was to compare the grading and prognostic value of l-[methyl-(11)C]-methionine ((11)C-MET) PET in glioma patients with (18)F-FDG PET and contrast-enhanced MRI. METHODS: Patients (n = 102) with histopathologically confirmed gliomas were followed up for an average of 34.6 ± 3.8 mo after PET. The median survival was 18 ± 4.7 mo in the high-grade glioma group and 58 ± 27 mo in the low-grade glioma group. Patients underwent (18)F-FDG PET, (11)C-MET PET, and MRI in the diagnostic and preoperative stage. The ratio of the mean standardized uptake value in the tumor to mean standardized uptake value in contralateral normal cortex (T/N ratio) was calculated. Kaplan-Meier survival analysis and ANOVA were performed. RESULTS: T/N ratios for (11)C-MET PET and (18)F-FDG PET were significantly higher in high-grade gliomas than in low-grade gliomas (2.15 ± 0.77 vs. 1.56 ± 0.74, P < 0.001, and 0.85 ± 0.61 vs. 0.63 ± 0.37, P < 0.01, respectively). Median survival was 19 ± 5.4 mo in patients with a T/N ratio greater than 1.51 for (11)C-MET PET and 58 ± 26.7 mo in those with a T/N ratio less than 1.51 (P = 0.03). Among the LGGs, median survival was lower in patients with a mean T/N ratio greater than 1.51 for (11)C-MET PET (16 ± 10 mo; 95% confidence interval, 1-36 mo) than in those with a T/N ratio less than 1.51 (P = 0.04). No significant difference in survival in LGGs was based on (18)F-FDG uptake and MRI contrast enhancement. CONCLUSION: (11)C-MET PET can predict prognosis in gliomas and is better than (18)F-FDG PET and MRI in predicting survival in LGGs.

Advanced adenoma diagnosis with FDG PET in a visibly normal mucosa: a case report.

BACKGROUND: An accurate, early diagnosis and treatment of adenomatous polyp can curtail progression to colorectal cancer. F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) reveals the biochemical changes associated with the development of many cancers which precede the appearance of gross anatomical changes that may be visualized during surgical resection or via imaging with MR or CT. INTERVENTION: We detail the history of a 64 year old female who had a whole-body FDG PET scan as a part of an employee wellness program. A dose of 12.2 mCi of F-18 labeled FDG was administered. RESULTS: A focal cecal uptake with a standardized uptake value (SUV) of 8.9 was found on the PET scan. Conversely, only normal mucosa was observed during a colonoscopy done 2 months after the PET scan. Motivated by the PET scan finding, the colonoscopist performed a biopsy which revealed a villous adenoma without high grade dysplasia. Pathology from tissue extracted during an exploratory laparatomy completed one month later found the lesion to be a villous adenoma with high grade dysplasia. CONCLUSION: Whole-body FDG PET scan revealed the biochemical metabolic changes in malignancy that preceded the appearance of any gross anatomical abnormality. A positive FDG PET scan indicative of colorectal cancer should be followed up with a colonoscopy and biopsy even in a visibly normal mucosa.

Image guidance during abdominal exploration for recurrent colorectal cancer.

BACKGROUND: Real-time intraoperative image guidance has been successfully applied to malignancies of the head, neck and central nervous system. Few attempts have been made to apply this technology to gastrointestinal cancers. Our purpose was to determine if a computer-assisted navigation system could be accurately used at the time of abdominal exploration. METHODS: Fourteen patients with resectable recurrent colorectal cancer underwent computer tomography (CT) imaging of the abdomen and pelvis. The CT images were uploaded to a StealthStation (Medtronic, Inc., Minneapolis, MN), a device that tracks the motion of a handheld probe in the operating field and displays its position, in real time, on the uploaded images. Various anatomic points were utilized to match, or register, the patient to the images in the navigation system. After four or more anatomic points were registered, the accuracy of the registration process was computed by the navigation system and reported as the global error. RESULTS: A total of 23 different anatomic structures were used for registration. The median number of points used for registration per patient was 6.5 (range 5-9). The anatomic sites most commonly used were the anterior superior iliac spines, aortic bifurcation, sacral promontory, symphysis pubis, and iliac artery bifurcation. The median global error was 10.0 mm (range 6.7 mm-27.0 mm). CONCLUSION: Computer-assisted navigation systems can be used to accurately deliver image guidance at the time of abdominal exploration. Future work will be directed at determining the value of this technology in the localization and resection of tumors.