Hybrid MR-PET of brain tumours using amino acid PET and chemical exchange saturation transfer MRI.

PURPOSE: PET using radiolabelled amino acids has become a promising tool in the diagnostics of gliomas and brain metastasis. Current research is focused on the evaluation of amide proton transfer (APT) chemical exchange saturation transfer (CEST) MR imaging for brain tumour imaging. In this hybrid MR-PET study, brain tumours were compared using 3D data derived from APT-CEST MRI and amino acid PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). METHODS: Eight patients with gliomas were investigated simultaneously with 18F-FET PET and APT-CEST MRI using a 3-T MR-BrainPET scanner. CEST imaging was based on a steady-state approach using a B1 average power of 1µT. B0 field inhomogeneities were corrected a Prametric images of magnetisation transfer ratio asymmetry (MTRasym) and differences to the extrapolated semi-solid magnetisation transfer reference method, APT# and nuclear Overhauser effect (NOE#), were calculated. Statistical analysis of the tumour-to-brain ratio of the CEST data was performed against PET data using the non-parametric Wilcoxon test. RESULTS: A tumour-to-brain ratio derived from APT# and 18F-FET presented no significant differences, and no correlation was found between APT# and 18F-FET PET data. The distance between local hot spot APT# and 18F-FET were different (average 20 ± 13 mm, range 4-45 mm). CONCLUSION: For the first time, CEST images were compared with 18F-FET in a simultaneous MR-PET measurement. Imaging findings derived from18F-FET PET and APT CEST MRI seem to provide different biological information. The validation of these imaging findings by histological confirmation is necessary, ideally using stereotactic biopsy.

Methods for molecular imaging of brain tumours in a hybrid MR-PET context: Water content, T2∗, diffusion indices and FET-PET.

The aim of this study is to present and evaluate a multiparametric and multi-modality imaging protocol applied to brain tumours and investigate correlations between these different imaging measures. In particular, we describe a method for rapid, non-invasive, quantitative imaging of water content of brain tissue, based on a single multiple-echo gradient-echo (mGRE) acquisition. We include in the processing a method for noise reduction of the multi-contrast data based on Principal Component Analysis (PCA). Noise reduction is a key ingredient to obtaining high-precision water content and transverse relaxation T2∗ values. The quantitative method is applied to brain tumour patients in a hybrid MR-PET environment. Active tumour tissue is identified by means of FET-PET; oedema, white and grey-matter segmentation is performed based on MRI contrasts. Water content information is not only relevant by itself, but also as a basis for correlations with other quantitative measures of water behaviour in tissue and interpreting the microenvironment of water. Water content in active tumour tissue (84%) and oedema (79%) regions is found to be higher than that of normal WM (69%) and close to that of normal GM (83%). Consistent with literature reports, mean kurtosis is measured to be lower in tumour and oedema regions than in normal WM and GM, whereas mean diffusivity is increased. Voxel-based correlations between water content and diffusion indices obtained with diffusion kurtosis tensor imaging, and between quantitative MRI and FET-PET are reported for 8 brain tumour patients. The effective transverse relaxation time T2∗ is found to be the MR parameter showing the strongest correlations with other MR indices derived here and with FET-PET.

Meningioangiomatosis in a patient with progressive focal neurological deficit-case report and review of literature.

Meningioangiomatosis (MA) represents a vascular hamartoma accompanied by meningothelial cell proliferation. It generally becomes symptomatic with difficult to control seizures, though in some patients it may be asymptomatic. We present the case of a 41-year-old male patient with a newly developed central distal monoparesis of the left leg. Cranial magnetic resonance imaging (MRI) and further diagnostic characterization via (18)F-Fluoro-Ethyl-Tyrosine positron emission tomography ((18)F-FET-PET) indicated a low-grade glioma. Histopathological diagnosis revealed a meningioangiomatosis. The clinical, radiological and neuropathological findings of this rare constellation are described and discussed with the actual literature.

Integrated boost IMRT with FET-PET-adapted local dose escalation in glioblastomas. Results of a prospective phase II study.

PURPOSE: Dose escalations above 60 Gy based on MRI have not led to prognostic benefits in glioblastoma patients yet. With positron emission tomography (PET) using [(18)F]fluorethyl-L-tyrosine (FET), tumor coverage can be optimized with the option of regional dose escalation in the area of viable tumor tissue. METHODS AND MATERIALS: In a prospective phase II study (January 2008 to December 2009), 22 patients (median age 55 years) received radiochemotherapy after surgery. The radiotherapy was performed as an MRI and FET-PET-based integrated-boost intensity-modulated radiotherapy (IMRT). The prescribed dose was 72 and 60 Gy (single dose 2.4 and 2.0 Gy, respectively) for the FET-PET- and MR-based PTV-FET((72 Gy)) and PTV-MR((60 Gy)). FET-PET and MRI were performed routinely for follow-up. Quality of life and cognitive aspects were recorded by the EORTC-QLQ-C30/QLQ Brain20 and Mini-Mental Status Examination (MMSE), while the therapy-related toxicity was recorded using the CTC3.0 and RTOG scores. RESULTS: Median overall survival (OS) and disease-free survival (DFS) were 14.8 and 7.8 months, respectively. All local relapses were detected at least partly within the 95% dose volume of PTV-MR((60 Gy)). No relevant radiotherapy-related side effects were observed (excepted alopecia). In 2 patients, a pseudoprogression was observed in the MRI. Tumor progression could be excluded by FET-PET and was confirmed in further MRI and FET-PET imaging. No significant changes were observed in MMSE scores and in the EORTC QLQ-C30/QLQ-Brain20 questionnaires. CONCLUSION: Our dose escalation concept with a total dose of 72 Gy, based on FET-PET, did not lead to a survival benefit. Acute and late toxicity were not increased, compared with historical controls and published dose-escalation studies.

[Use of amino acid PET in the Diagnostic and Treatment Management of cerebral gliomas]. / Anwendung der Aminosäure-PET in der Diagnostik und Therapie von zerebralen Gliomen.

Structural as well as functional imaging methods are of special importance in neurooncology. Improvements of radionuclide and magnetic resonance-based imaging modalities over the past decade have enabled clinicians to non-invasively assess the dynamics of disease-specific processes at the molecular level in patients with malignant gliomas. To date, a range of complementary imaging parameters have been established in the diagnostic work-up of patients with brain tumours. Magnetic resonance imaging (MRI) provides morphological information as well as functional information such as vascular permeability, cell density, tumour perfusion, and metabolic information by using magnetic resonance spectroscopy. The use of radiolabelled amino acids for positron emission tomography (PET) allows a better delineation of tumour margins and improves targeting of biopsy and radiotherapy, and planning surgery. In addition, amino acid imaging appears useful in distinguishing tumour recurrence from non-specific post-therapeutic scar tissue, in predicting prognosis in low-grade gliomas, and in monitoring metabolic response during treatment. Taken together, MRI and PET provide complementary information about tumour biology and activity, thereby resulting in an improved understanding of the kinetics of tumour growth and therefore allow new insights into the pathophysiology of malignant brain tumours. However, multimodal imaging studies comparing the value of amino acid PET and functional methods of MRI (e. g., perfusion and diffusion weighted imaging) are needed. From these studies, surrogate MRI and PET imaging techniques need to be derived to gain complementary structural and functional information of brain tumours that can be placed into common clinical practice which will optimise the clinical management of patients with malignant gliomas.

[German guidelines for brain tumour imaging by PET and SPECT using labelled amino acids]. / PET- und SPECT-Untersuchungen von Hirntumoren mit radioaktiv markierten Aminosäuren.

For the primary diagnosis of brain tumours, morphological imaging by means of magnetic resonance imaging (MRI) is the current method of choice. The complementary use of functional imaging by positron emitting tomography (PET) and single photon emitting computerized tomography (SPECT) with labelled amino acids can provide significant information on some clinically relevant questions, which are beyond the capacity of MRI. These diagnostic issues affect in particular the improvement of biopsy targeting and tumour delineation for surgery and radiotherapy planning. In addition, amino acid labelled PET and SPECT tracers are helpful for the differentiation between tumour recurrence and non-specific post-therapeutic tissue changes, in predicting prognosis of low grade gliomas, and for metabolic monitoring of treatment response. The application of dynamic PET examination protocols for the assessment of amino acid kinetics has been shown to enable an improved non-invasive tumour grading. The purpose of this guideline is to provide practical assistance for indication, examination procedure and image analysis of brain PET/SPECT with labelled amino acids in order to allow for a high quality standard of the method. After a short introduction on pathobiochemistry and radiopharmacy of amino acid labelled tracers, concrete and detailed information is given on the several indications, patient preparation and examination protocols as well as on data reconstruction, visual and quantitative image analysis and interpretation. In addition, possible pitfalls are described, and the relevant original publications are listed for further information.

High resolution BrainPET combined with simultaneous MRI.

UNLABELLED: After the successful clinical introduction of PET/CT, a novel hybrid imaging technology combining PET with the versatile attributes of MRI is emerging. At the Forschungszentrum Jülich, one of four prototypes available worldwide combining a commercial 3T MRI with a newly developed BrainPET insert has been installed, allowing simultaneous data acquisition with PET and MRI. The BrainPET is equipped with LSO crystals of 2.5 mm width and Avalanche photodiodes (APD) as readout electronics. Here we report on some performance characteristics obtained by phantom studies and also on the initial BrainPET studies on various patients as compared with a conventional HR+ PET-only scanner. MATERIAL, METHODS: The radiotracers [18F]-fluoro-ethyl-tyrosine (FET), [11C]-flumazenil and [18F]-FP-CIT were applied. RESULTS: Comparing the PET data obtained with the BrainPET to those of the HR+ scanner demonstrated the high image quality and the superior resolution capability of the BrainPET. Furthermore, it is shown that various MR images of excellent quality could be acquired simultaneously with BrainPET scans without any relevant artefacts. DISCUSSION, CONCLUSION: Initial experiences with the hybrid MRI/BrainPET indicate a promising basis for further developments of this unique technique allowing simultaneous PET imaging combined with both anatomical and functional MRI.

Multimodal Fingerprints of Resting State Networks as assessed by Simultaneous Trimodal MR-PET-EEG Imaging.

Simultaneous MR-PET-EEG (magnetic resonance imaging - positron emission tomography - electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here for the first time. It enables the assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. Here, we characterize the brain's default mode network (DMN) in healthy male subjects using multimodal fingerprinting by quantifying energy metabolism via 2- [18F]fluoro-2-desoxy-D-glucose PET (FDG-PET), the inhibition - excitation balance of neuronal activation via magnetic resonance spectroscopy (MRS), its functional connectivity via fMRI and its electrophysiological signature via EEG. The trimodal approach reveals a complementary fingerprint. Neuronal activation within the DMN as assessed with fMRI is positively correlated with the mean standard uptake value of FDG. Electrical source localization of EEG signals shows a significant difference between the dorsal DMN and sensorimotor network in the frequency range of δ, θ, α and ß-1, but not with ß-2 and ß-3. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.

Bone regeneration induced by a 3D architectured hydrogel in a rat critical-size calvarial defect.

Bone regeneration can be stimulated by implantation of biomaterials, which is especially important for larger bone defects. Here, healing potency of the porous ArcGel was evaluated in a critical-size calvarial bone defect in rats in comparison with clinical standard autologous bone and Bio-Oss® Collagen (BioOss), a bone graft material frequently used in clinics. Bone healing and metabolic processes involved were monitored longitudinally by [18F]-fluoride and [18F]-FDG µ-PET/CT 1d, 3d, 3w, 6w, and 12w post implantation. Differences in quality of bone healing were assessed by ex vivo µ-CT, mechanical tests and histomorphometry. The amount of bone formed after implantation of ArcGel was comparable to autologous bone and superior to BioOss (histomorphometry). Furthermore, microarchitecture of newly formed bone was more physiological and better functional in case of ArcGel (push-out tests). [18F]-FDG uptake increased until 3d after implantation, and decreased until 12w for both ArcGel and BioOss. [18F]-fluoride uptake increased until 3w post implantation for all materials, but persisted significantly longer at higher levels for BioOss, which indicates a prolonged remodelling phase. The study demonstrates the potential of ArcGel to induce restitutio ad integrum comparable with clinical standard autologous bone and better bone regeneration in large defects compared to a commercial state-of-the-art biomaterial.

Multimodal Imaging in Malignant Brain Tumors: Enhancing the Preoperative Risk Evaluation for Motor Deficits with a Combined Hybrid MRI-PET and Navigated Transcranial Magnetic Stimulation Approach.

BACKGROUND AND PURPOSE: Motor deficits in patients with brain tumors are caused mainly by irreversible infiltration of the motor network or by indirect mass effects; these deficits are potentially reversible on tumor removal. Here we used a novel multimodal imaging approach consisting of structural, functional, and metabolic neuroimaging to better distinguish these underlying causes in a preoperative setting and determine the predictive value of this approach. MATERIALS AND METHODS: Thirty patients with malignant brain tumors involving the central region underwent a hybrid O-(2-[(18)F]fluoroethyl)-L-tyrosine-PET-MR imaging and motor mapping by neuronavigated transcranial magnetic stimulation. The functional maps served as localizers for DTI tractography of the corticospinal tract. The spatial relationship between functional tissue (motor cortex and corticospinal tract) and lesion volumes as depicted by structural and metabolic imaging was analyzed. RESULTS: Motor impairment was found in nearly all patients in whom the contrast-enhanced T1WI or PET lesion overlapped functional tissue. All patients who functionally deteriorated after the operation showed such overlap on presurgical maps, while the absence of overlap predicted a favorable motor outcome. PET was superior to contrast-enhanced T1WI for revealing a motor deficit before the operation. However, the best correlation with clinical impairment was found for T2WI lesion overlap with functional tissue maps, but the prognostic value for motor recovery was not significant. CONCLUSIONS: Overlapping contrast-enhanced T1WI or PET-positive signals with motor functional tissue were highly indicative of motor impairment and predictive for surgery-associated functional outcome. Such a multimodal diagnostic approach may contribute to the risk evaluation of operation-associated motor deficits in patients with brain tumors.

Applications of PET imaging of neurological tumors with radiolabeled amino acids.

Routine diagnostics and treatment monitoring of brain tumors is usually based on contrast-enhanced magnetic resonance imaging (MRI). However, the capacity of structural MRI to differentiate neoplastic tissue from non-specific treatment changes may be limited especially after therapeutic interventions such as neurosurgical resection, radio- and chemotherapy. Metabolic imaging using PET may provide relevant additional information on tumor metabolism, which allows for more accurate diagnostics especially in clinically equivocal situations. In contrast to the widely used ¹8F-2-fluoro-2-deoxy-D-glucose, which exhibits a poor tumor-to-background contrast within the brain, amino acid tracers provide high sensitivity to detect primary tumors, recurrent or residual gliomas, including most low-grade gliomas. The method improves targeting of biopsy and provides additional information of tumor extent, which is helpful for planning neurosurgery and radiotherapy. In the further course of the disease, amino acid positron-emission tomography (PET) allows a sensitive monitoring of treatment response, the early detection of tumor recurrence, and an improved differentiation of tumor recurrence from treatment-related changes. In the past, the method had only limited availability due to the use of radiopharmaceuticals with a short half-life. In recent years, however, novel amino acid tracers labeled with positron emitters with a longer half-life have been developed and clinically validated which allow a more efficient and cost-effective application. These developments and the well-documented diagnostic performance of PET using radiolabeled amino acids suggest that its application continues to spread and that the method may be available as a routine diagnostic technique for certain indications in the near future.

Tomographic studies of rCBF with [99mTc]-HM-PAO SPECT in patients with brain tumors: comparison with C15O2 continuous inhalation technique and PET.

In 10 patients with malignant gliomas, the intracerebral distribution of [99mTc]-hexamethylpropylene-amine oxime [( 99mTc]-HM-PAO) was studied with single photon emission computed tomography (SPECT) in comparison with C15O2 steady-state inhalation technique to measure cerebral blood flow using positron emission tomography (PET). In all instances, the cerebral [99mTc]-HM-PAO distribution was comparable with the regional pattern of cerebral blood flow (rCBF) observed with PET. This was confirmed by a significant correlation of tumor to cortex and tumor to white matter ratios between these two experimental methods. However, the contrast between high and low activity regions in the SPECT scans was significantly less than that in the PET scans. Contrast enhancement of the SPECT scans was accomplished using a correction formula proposed by Lassen.

Transport mechanisms of 3-[123I]iodo-alpha-methyl-L-tyrosine in a human glioma cell line: comparison with [3H]methyl]-L-methionine.

UNLABELLED: The amino acid analog 3-[(123)I]iodo-alpha-methyl-L-tyrosine (IMT) is under clinical evaluation as a SPECT tracer of amino acid transport in brain tumors. This study investigated the carrier systems involved in IMT transport in human glioma cells in comparison with [3H-methyl]-L-methionine (3H-MET). METHODS: Human glioma cells, type 86HG-39, were cultured and incubated for 1 min at 37 degrees C with IMT and 3H-MET in the lag phase (1.2 d after seeding), exponential growth phase (3 d after seeding), and plateau phase (8 d after seeding). Experiments were performed in the presence and absence of Na+, during inhibition of system L amino acid transport by 2-aminobicyclo[2.2.1 ]heptane-2-carboxylic acid (BCH), and during inhibition of system A amino acid transport by 2-(methylamino)-isobutyric acid (MeAIB). RESULTS: IMT and 3H-MET uptake decreased by 55%-73% when the cells entered from the exponential growth phase into the plateau phase (P< 0.05; n = 3-11). Inhibition by BCH reduced uptake of IMT in the lag phase, exponential growth phase, and plateau phase by 90%-98% (P < 0.001; n = 3-6) and the uptake of 3H-MET by 73%-83% (P < 0.001; n = 3-11). In a Na+-free medium 3H-MET uptake was reduced by 23%-33% (P < 0.05; n = 3-11), whereas IMT uptake was not significantly different. MeAIB showed no significant effect on IMT or 3H-MET uptake in either phase. CONCLUSION: Transport of both IMT and 3H-MET depends on the proliferation rate of human glioma cells in vitro and is dominated by BCH-sensitive transport. These data indicate that system L is induced in rapidly proliferating glioma cells and is the main contributor to the uptake of both tracers. 3H-MET transport showed a minor Na+ dependency that was not attributable to system A. The similarity of transport mechanisms of both tracers emphasizes the clinical equivalence of IMT SPECT and (11)C-MET PET for the diagnostic evaluation of gliomas.

A cell-culture reactor for the on-line evaluation of radiopharmaceuticals: evaluation of the lumped constant of FDG in human glioma cells.

UNLABELLED: A fluidized-bed cell-culture reactor with on-line radioactivity detection was developed for the in vitro evaluation of radiopharmaceuticals. The technique was applied to measure the dependency of the lumped constant (LC) of FDG on the glucose concentration in the culture medium in a human glioma cell line. METHODS: Human glioblastoma cells (86HG39) immobilized in open porous microcarriers were cultivated in a continuously operating fluidized-bed bioreactor. At different glucose concentrations in the culture medium, step inputs (0.1 MBq/mL) of FDG were performed and the cellular uptake of FDG was measured on-line and compared with analyzed samples. From these results, the LC of FDG and its dependency on the glucose concentration were calculated. RESULTS: This fluidized-bed technique enabled precise and reproducible adjustment of all relevant experimental parameters, including radiotracer time-concentration course, medium composition, pH, dissolved oxygen and temperature under steady-state conditions, and an on-line determination of the intracellular radiotracer uptake. The immobilized glioma cells formed stable, 3-dimensional, tumor-like spheroids and were continuously proliferating, as proven by an S-phase portion of 25%-40%. For further examination of the cells, an enzymatic method for detachment from the carriers without cellular destruction was introduced. In the FDG experiments, a significant dependency of the LC on the glucose level was found. For normoglycemic glucose concentrations, the LC was determined to be in the range of 0.7+/-0.1, whereas in hypoglycemia LC increased progressively up to a value of 1.22+/-0.01 at a glucose concentration of 3 mmol/L. CONCLUSION: The bioreactor represents an improved in vitro model for the on-line evaluation of radiotracers and combines a wide range of experimental setups and 3-dimensional, tissue-like cell cultivation with a technique for on-line radioactivity detection.

Technetium-99m-HMPAO, technetium-99m-ECD and iodine-123-IMP cerebral blood flow measurements with pharmacological interventions in primates.

UNLABELLED: Technetium-99m-bicisate ethyl cysteinate dimer (ECD) presents a different pattern from cerebral blood flow (CBF) in the subacute phase of cerebral infarction, as measured by PET, perhaps due to lack of oxygen and enzyme activity; this pattern is contrary to that of hexamethyl-propyleneamine oxime (HMPAO) but similar to that of N-isopropyl-[123I]beta-iodoamphetamine ([123I]IMP). This study explores possible CBF differences among HMPAO, ECD and IMP, with various relevant drug interventions. METHODS: Anesthetized adult baboons were used in these SPECT studies. Four studies (n = 6 baboons for each study), one control study and three intervention studies involving intravenous acetazolamide, nimodipine infusion and intramuscular sumatriptan, were followed with 99mTc-HMPAO, 99mTc-ECD and [123I]IMP. The split-dose method was used as follows. For each tracer, intervention data from the second SPECT (SPECT-2) after the second tracer injection (444 MBq) reflected a change in CBF with respect to the baseline SPECT (SPECT-1) data from the initial injection (222 MBq). These changes as a ratio, R (R = SPECT-2/SPECT-1), for each study, and the R values for each tracer were compared to R values from the corresponding control studies, yielding a quantitative estimate of drug effects. RESULTS: There were no significant differences (p > 0.05) between HMPAO and ECD for the control, acetazolamide and sumatriptan studies, but there was indeed a difference between the two for the nimodipine study, indicating a nimodipine-dependent underestimation of CBF with ECD (and also with IMP), with respect to HMPAO. A further significant difference was that larger CBF increases were observed with acetazolamide, as measured with [123I]IMP. CONCLUSION: This is a crucial observation for the clinical interpretation of CBF SPECT data and should direct the choice of tracer for a specific examination.

Brain and brain tumor uptake of L-3-[123I]iodo-alpha-methyl tyrosine: competition with natural L-amino acids.

SPECT studies with L-3-[123I]iodo-alpha-methyl tyrosine (IMT) were carried out in 10 patients with different types of brain tumors--first under fasting conditions (basal) and a week later during intravenous infusion of a mixture of naturally-occurring L-amino acids (AA load). An uptake index (UI) was calculated by dividing tissue count rates by the integral of plasma count rates. The UI decreased by 45.6% +/- 15.4% (n = 10, p less than 0.001) for normal brain and by 53.2% +/- 14.1% for gliomas (n = 5, p less than 0.01) during AA load compared to basal conditions, while two meningiomas and a metastasis showed only a minor decrease (23.9 +/- 5.7%, n.s.). Two pituitary adenomas could not be delineated on the SPECT scans. These data indicate that IMT competes with naturally-occurring L-amino acids for transport into normal brain and gliomas. Transport characteristics of IMT into tumors of nonglial origin appear to be different from those of gliomas. For both types of tumors, it is advisable to perform IMT-SPECT under fasting conditions.

The influence of plasma glucose levels on fluorine-18-fluorodeoxyglucose uptake in bronchial carcinomas.

PET studies with 2-18F-fluorodeoxyglucose (FDG) were carried out in 15 patients with bronchial carcinomas, first under fasting conditions and then 2 days later during intravenous infusion of a 20% glucose solution which raised the plasma glucose level from 84.6 +/- 14.7 to 168.3 +/- 23.6 mg/100 ml (n = 15, p < 0.001). Tumor metabolism was quantified by the dose absorption ratio (DAR) of FDG uptake [DAR = tissue concentration/(injected dose/body weight)] and also by the rate of glucose consumption (MR) as measured by the Patlak graphical approach in 12 patients. The DAR decreased from 5.07 +/- 1.89 under fasting conditions to 2.84 +/- 0.97 (-41.8% +/- 15%, n = 15, p < 0.001) during glucose infusion, while the MR remained constant (4.71 +/- 2.38 mg/100 ml/min versus 4.96 +/- 2.46 mg/100 ml/min, n = 12, ns). Correction of the DAR data by plasma glucose level eliminated the significant difference between the fasting and glucose load [4.24 +/- 1.59 versus 4.70 +/- 1.45 (n = 15, ns)], but considerable changes in individual patients remained. These data indicate that the DAR of FDG uptake in bronchial carcinomas is influenced significantly by plasma glucose levels. Dynamic quantification of glucose metabolism using the Patlak approach is less dependent on the plasma glucose level and appears advantageous when high reproducibility is needed.

3-[123I]iodo-alpha-methyltyrosine and [methyl-11C]-L-methionine uptake in cerebral gliomas: a comparative study using SPECT and PET.

UNLABELLED: This study compares the uptake of the nonmetabolizable amino acid analog 3-[123I]iodo-alpha-methyltyrosine (IMT) and of [methyl-11C]-L-methionine (MET) in cerebral gliomas. METHODS: In 14 patients with cerebral gliomas, IMT uptake was measured using SPECT (10 dynamic, 4 static SPECT acquisitions) and, on the same day, MET uptake by dynamic PET. The IMT and MET data were compared with respect to tracer kinetics, tumor to brain ratios (T/B) and tumor size after converting the resolution of the PET scans to that of the SPECT scans (14 mm FWHM). RESULTS: All gliomas showed increased uptake of both tracers in relation to normal brain tissue. Visual comparison of the scans yielded no differences in tumor size and shape with both methods. IMT showed a maximal tracer uptake in brain and in tumors at about 15 min postinjection which was followed by a washout of 45.0% +/- 13.5% in gliomas (mean +/- s.d., p < 0.001, n = 10) and 35.3% +/- 5.4% in normal brain (p < 0.001, n = 10) at 60 min postinjection. MET concentration in tumor tissue or brain tissue between 15 and 60 min remained constant. T/B ratios of IMT SPECT and MET PET showed a significant correlation at 15 min postinjection (r = 0.69, n = 10, p = 0.03), a low correlation for the mean values of the scans from 15-60 min postinjection (r = 0.54, n = 14, p = 0.05) and no correlation at 60 min postinjection (r = 0.09, n = 10, n.s.). CONCLUSION: IMT and MET uptake in gliomas is similar in the early, transport dominated phase. There are some differences in tumor to brain ratios between both tracers within the first hour postinjection that are mainly caused by variable washout of IMT. Imaging of tumor extent with IMT SPECT is comparable to MET PET. Thus, amino acid SPECT using IMT is a promising tool to evaluate the biological activity and intracerebral infiltration of gliomas.

Comparison of iodotyrosines and methionine uptake in a rat glioma model.

UNLABELLED: This study compares brain tumor imaging with 3-[123I]iodo-alpha-methyl-L-tyrosine (IMT) and 3-[123I/125I]iodo-O-methyl-alpha-methyl-L-tyrosine (OMIMT) to that with [methyl-3H]-L-methionine (Met) in a rat glioma model by double-tracer autoradiography. METHODS: Cells of the glioma clone F-98 were implanted stereotactically into the right basal ganglia of 22 Fischer 344 rats. After 8 days of tumor growth, the animals simultaneously were injected with a mixture of either 123I-IMT and 3H-Met (n=5), 123I-OMIMT and 3H-Met (n=8) or 123I-IMT and 125I-OMIMT (n=9). The animals were killed 15 min after the tracer injection and cryosections of the tumor-bearing brain area were exposed to phosphor-imaging plates both immediately and after the decay of 123I. Tumor-to-brain ratios (T/B) and intratumoral distribution of the different tracers and of the cresyl violet staining of the tissue were compared. RESULTS: There was a significant correlation of the T/B ratios between all tracers (IMT versus Met: r=0.97, n=5, p < 0.01; OMIMT versus Met: r=0.94, n=8, p < 0.001; OMIMT versus IMT: r=0.95, n=9, p < 0.001). Intratumoral tracer distribution was similar for all tracers and the extent of tumor labeling was identical to that of the histological tumor extent. Mean values of the T/B ratios, however, were lower for IMT (2.81+/-0.78, n=14, mean+/-s.d., p < 0.01 compared with Met) and for OMIMT (2.03+/-0.57, n=17, p < 0.01 compared with Met) than for Met (3.86+/-1.12, n=13). CONCLUSION: This study confirms that tumor imaging with IMT is similar to that of Met but T/B ratios of IMT are lower. OMIMT intratumoral tracer distribution and tumor size are similar to Met and IMT, but the T/B contrast is rather low and makes this amino acid less suitable for clinical application.

Radiolabeled amino acids: basic aspects and clinical applications in oncology.

As the applications of metabolic imaging are expanding, radiolabeled amino acids may gain increased clinical interest. This review first describes the basic aspects of amino acid metabolism, then continues with basic aspects of radiolabeled amino acids, and finally describes clinical applications, with an emphasis on diagnostic value. A special focus is on (11)C-methionine, (11)C-tyrosine, and (123)I-iodomethyltyrosine, because these have been most used clinically, although their common affinity for the L-transport systems may limit generalization to other classes of amino acids. The theoretic and preclinical background of amino acid imaging is sound and supports clinical applications. The fact that amino acid imaging is less influenced by inflammation may be advantageous in comparison with (18)F-FDG PET imaging, although tumor specificity is not absolute. In brain tumor imaging, the use of radiolabeled amino acids is established, the diagnostic accuracy of amino acid imaging seems adequate, and the diagnostic value seems advantageous. The general feasibility of amino acid imaging in other tumor types has sufficiently been shown, but more research is required in larger patient series and in well-defined clinical settings.