fluoroethyl)-L-tyrosine Positron Emission Tomography Research Articles

P05.02.A PRELIMINARY FINDINGS FROM THE MRI QUALITY ASSURANCE PROGRAMME FOR THE PROSPECTIVE MULTI-SITE AUSTRALIAN FIG ([FET-PET IN GLIOBLASTOMA) TROG 18.06 STUDY

Abstract BACKGROUND The O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) in Glioblastoma (FIG) study is a prospective study evaluating the management impact of FET-PET imaging in up to 210 newly diagnosed adult glioblastoma patients across 10 Australian sites. Patients undergo contrast MRI and FET-PET at 3 timepoints: pre-chemoradiotherapy (CRT), one-month post-CRT and at suspected progression. MRI QA programme components, approach and integrated workflows are described here. MATERIAL AND METHODS The FIG MRI protocol comprised 3D-T1, 3D-FLAIR, Axial 2D DWI (including derived ADC map), DCE (including T1 mapping), DSC, Axial T2 and 3D T1-post-contrast (T1C) sequences, with SWI and 3D DIR sequences optional. QA components included data acquisition quality and completeness (standard and advanced), motion artefact, low contrast to noise or signal to noise, series description and susceptibility artifacts. Suitability of T1/T1C using modified RANO (mRANO) criteria was assessed. An optimised workflow involved site upload from local PACS systems to centralised database via TROG Central Quality Management System (CQMS) platform and collation into a central imaging database utilising MIM software. The MRI QA workflow encompassed automated anonymisation of DICOM data, data completeness and reconstruction evaluation, then review by two expert neuroimaging analysts. Sites received feedback with request for resubmission where required. RESULTS Between December 2021 and February 2023, MRI data in 74 patients across 9 sites with median of 6 patients (range 2-17) per site was submitted. A total of 141 MRI datasets across all timepoints were collected (per site range:4-35, median:13), with 43 imaging time-points selected for QA (per site range:3-12, median: 4). Importantly, 41/43 (95%) of initial datasets were deemed suitable for mRANO assessment, but only 13/43 (30%) were suitable for advanced MRI analysis. Very few datasets had motion or susceptibility artifacts, low contrast to noise or signal to noise, or incorrect series description. Technical issues identified included incomplete data (DCE - missing T1 maps, DWI - missing ADC maps), incorrect sequence reconstruction (DCE split series and Axial/Sagittal/Coronal reformats for 3D images) and lack of non-mandatory SWI sequences. Feedback to sites resulted in improvements in DCE sequence acquisition from split series in 11/45 (24%) to preferred single series in 18/24 (75%) and similar increases in T1 maps completeness from 7/19 (37%) to 7/7 (100%). CONCLUSION Despite challenges in multisite workflow and substantial multi-modality site and central data management, a robust MRI QA program has confirmed 95% compliance for mRANO assessment. Site specific feedback resulted in increased compliance with advanced MRI sequences to enable detailed future analysis.

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

Simple SummaryPET using radiolabelled amino acids has become an essential tool for diagnosing brain tumours in addition to MRI. O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is one of the most successful tracers in the field. We analysed our database of 6534 FET PET examinations regarding the diagnostic needs and preferences of the referring physicians for FET PET in the clinical decision-making process. The demand for FET PET increased considerably in the last decade, especially for differentiating tumour progress from treatment-related changes in gliomas. Accordingly, referring physicians rated the diagnostics of recurrent glioma and recurrent brain metastases as the most relevant indication for FET PET. The analysis and survey results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for approval for routine use.O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians’ rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

NIMG-49. A PROSPECTIVE, MULTI-CENTRE TRIAL OF FET-PET IN GLIOBLASTOMA PATIENTS - THE TROG 18.06 FIG STUDY: KEY ASPECTS OF IMAGING AND RADIATION ONCOLOGY CREDENTIALING

Abstract The FIG study is a prospective non-randomised study now recruiting up to 210 newly diagnosed GBM participants across ten Australian sites. Study outcomes will address the role of [18F] fluoroethyl-L-tyrosine positron emission tomography (FET-PET) in radiotherapy (RT) planning, evaluation of post-treatment changes versus disease progression and prognostication. We describe here the methodology and preliminary outcomes for site credentialing. Eligible participants with GBM undergo FET-PET imaging at three time-points: FET-PET1-post-operative pre-chemo-RT, FET-PET2 acquired one month post-chemo-RT and FET-PET3 (+/-FDG-PET) triggered when clinical and/or radiological (MRI) progression is suspected. Dynamic and static FET-PET images are analysed qualitatively and quantitatively. Radiotherapy is as per standard care with the treating Radiation Oncologist (RO) blinded to FET-PET1. Site nuclear medicine (NM) physicians are required to delineate a biological target volume (BTV) based on FET-PET1 with hybrid RT volumes derived post-hoc. Pre-trial NM quality assurance comprises certification from the Australasian Radiopharmaceutical Trials Network encompassing FET-PET radiochemistry Quality Control and PET camera calibration. Site and central integrated workflows incorporating multi-modality image registration, target volume/region of interest contouring and analysis have been developed. NM benchmarking involves delineation of FET-PET BTVs in 3 cases with another 3 cases addressing response criteria interpretation harmonized across FET-PET, FDG-PET and MRI. Site ROs complete 3 cases involving standard and hybrid target volume delineation based on pre-derived FET-PET volumes. All NM and RO credentialing cases undergo central expert review. To date, of six sites which have submitted full credentialing data, 19/21 RO and 6/6 planning cases were passed. Of 72 NM cases, 18/72 (25%) required resubmission, primarily related to ensuring standardisation of background regions and time activity curve interpretation. The FIG study will be pivotal in establishing the role of FET-PET in GBM management. The robust NM and RO credentialing program will build capacity and expertise in FET-PET production, acquisition and image interpretation.

Repeatability of image features extracted from FET PET in application to post-surgical glioblastoma assessment.

Positron emission tomography (PET) imaging using the amino acid tracer O-[2-(18F)fluoroethyl]-L-tyrosine (FET) has gained increased popularity within the past decade in the management of glioblastoma (GBM). Radiomics features extracted from FET PET images may be sensitive to variations when imaging at multiple time points. It is therefore necessary to assess feature robustness to test-retest imaging.Eight patients with histologically confirmed GBM that had undergone post-surgical test-retest FET PET imaging were recruited. In total, 1578 radiomic features were extracted from biological tumour volumes (BTVs) delineated using a semi-automatic contouring method. Feature repeatability was assessed using the intraclass correlation coefficient (ICC). The effect of both bin width and filter choice on feature repeatability was also investigated.59/106 (55.7%) features from the original image and 843/1472 (57.3%) features from filtered images had an ICC ≥ 0.85. Shape and first order features were most stable. Choice of bin width showed minimal impact on features defined as stable. The Laplacian of Gaussian (LoG, σ = 5 mm) and Wavelet filters (HLL and LHL) significantly improved feature repeatability (p ≪ 0.0001, p = 0.003, p = 0.002, respectively). Correlation of textural features with tumour volume was reported for transparency.FET PET radiomic features extracted from post-surgical images of GBM patients that are robust to test-retest imaging were identified. An investigation with a larger dataset is warranted to validate the findings in this study.

FET PET Radiomics for Differentiating Pseudoprogression from Early Tumor Progression in Glioma Patients Post-Chemoradiation.

Simple SummaryFollowing chemoradiation with alkylating agents in glioma patients, structural magnetic resonance imaging (MRI) may suggest tumor progression which subsequently improves during the course of the disease without any treatment change. This phenomenon has been termed pseudoprogression. Despite advances in medical imaging, a reliable diagnosis of pseudoprogression remains a challenging task. Radiomics is a subdiscipline of artificial intelligence and allows the identification and extraction of imaging features from various routine imaging modalities. These features can be used for the generation of mathematical models to improve diagnostics in patients with brain tumors. The present study highlights the potential of radiomics obtained from amino acid positron emission tomography (PET) for the diagnosis of pseudoprogression. In 34 patients with suspicious MRI early after chemoradiation completion, our radiomics model correctly identified all patients with pseudoprogression.Currently, a reliable diagnostic test for differentiating pseudoprogression from early tumor progression is lacking. We explored the potential of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) radiomics for this clinically important task. Thirty-four patients (isocitrate dehydrogenase (IDH)-wildtype glioblastoma, 94%) with progressive magnetic resonance imaging (MRI) changes according to the Response Assessment in Neuro-Oncology (RANO) criteria within the first 12 weeks after completing temozolomide chemoradiation underwent a dynamic FET PET scan. Static and dynamic FET PET parameters were calculated. For radiomics analysis, the number of datasets was increased to 102 using data augmentation. After randomly assigning patients to a training and test dataset, 944 features were calculated on unfiltered and filtered images. The number of features for model generation was limited to four to avoid data overfitting. Eighteen patients were diagnosed with early tumor progression, and 16 patients had pseudoprogression. The FET PET radiomics model correctly diagnosed pseudoprogression in all test cohort patients (sensitivity, 100%; negative predictive value, 100%). In contrast, the diagnostic performance of the best FET PET parameter (TBRmax) was lower (sensitivity, 81%; negative predictive value, 80%). The results suggest that FET PET radiomics helps diagnose patients with pseudoprogression with a high diagnostic performance. Given the clinical significance, further studies are warranted.

Correlation of Dynamic O-(2-[18F]Fluoroethyl)-L-Tyrosine Positron Emission Tomography, Conventional Magnetic Resonance Imaging, and Whole-Brain Histopathology in a Pretreated Glioblastoma: A Postmortem Study

Amino acid positron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) provides important additional information on the extent of viable tumor tissue of glioblastoma compared with magnetic resonance imaging (MRI). Especially after radiochemotherapy, progression of contrast enhancement in MRI is equivocal and may represent either tumor progression or treatment-related changes. Here, the first case comparing postmortem whole-brain histology of a patient with pretreated glioblastoma with dynamic invivo FET PET and MRI is presented. A 61-year-old patient with glioblastoma initially underwent partial tumor resection and died 11 weeks after completion of chemoradiation with concurrent temozolomide. Three days before the patient died, a follow-up FET PET and MRI scan indicated tumor progression. Autopsy was performed 48 hours after death. After formalin fixation, a 7-cm bihemispherical segment of the brain containing the entire tumor mass was cut into 3500 consecutive 20μm coronal sections. Representative sections were stained with hematoxylin and eosin stain, cresyl violet, and glial fibrillary acidic protein immunohistochemistry. An experienced neuropathologist identified areas of dense and diffuse neoplastic infiltration, astrogliosis, and necrosis. Invivo FET PET, MRI datasets, and postmortem histology were co-registered and compared by 3 experienced physicians. Increased uptake of FET in the area of equivocal contrast enhancement on MRI correlated very well with dense infiltration by vital tumor cells and showed tracer kinetics typical for malignant gliomas. An area of predominantly reactive astrogliosis showed only moderate uptake of FET and tracer kinetics usually observed in benign lesions. This case report impressively documents the correct imaging of a progressive glioblastoma by FET PET.

Imaging of amino acid transport in brain tumours: Positron emission tomography with O-(2-[18F]fluoroethyl)-L-tyrosine (FET).

The assessment of cerebral gliomas using magnetic resonance imaging (MRI) provides excellent structural images but cannot solve all diagnostic problems satisfactorily. The differentiation of tumour tissue from non-neoplastic changes may be difficult especially in the post-treatment phase. In recent years, positron emission tomography (PET) using radiolabelled amino acids has gained considerable interest as an additional tool to improve the diagnosis of cerebral gliomas and brain metastases. A key step for this advancement was the development of the F-18 labelled amino acid O-(2-[18F]fluoroethyl)-L-tyrosine (FET) which has spread rapidly in the last decade and replaced carbon-11 labelled amino acid tracers such as 11C-methyl-L-methionine (MET) in many centres in Europe. FET can be produced with high efficiency and distributed in a satellite concept like 2-[18F]fluoro-2-deoxy-D-glucose (FDG). Furthermore, FET exhibits favourable properties such as high in vivo stability, high tumour to background contrast and tissue specific tracer kinetics, which provides additional information for tumour grading or differential diagnosis. The Response Assessment in Neuro-Oncology (RANO) working group - an international effort to develop new standardized response criteria for clinical trials in brain tumours - has recently recommended the additional use of amino acid PET imaging for brain tumour management. FET PET can provide important diagnostic information in crucial situations such as the definition of biopsy site, the delineation of cerebral gliomas for therapy planning, sensitive monitoring of treatment response and an improved differentiation of tumour recurrence from treatment-related changes. In this article the basic information, methodological aspects and the actual status of clinical application of FET PET are reviewed.

Unsupervised consensus cluster analysis of [18F]-fluoroethyl-L-tyrosine positron emission tomography identified textural features for the diagnosis of pseudoprogression in high-grade glioma.

RationaleTimely detection of pseudoprogression (PSP) is crucial for the management of patients with high-grade glioma (HGG) but remains difficult. Textural features of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) mirror tumor uptake heterogeneity; some of them may be associated with tumor progression.MethodsFourteen patients with HGG and suspected of PSP underwent FET-PET imaging. A set of 19 conventional and textural FET-PET features were evaluated and subjected to unsupervised consensus clustering. The final diagnosis of true progression vs. PSP was based on follow-up MRI using RANO criteria.ResultsThree robust clusters have been identified based on 10 predominantly textural FET-PET features. None of the patients with PSP fell into cluster 2, which was associated with high values for textural FET-PET markers of uptake heterogeneity. Three out of 4 patients with PSP were assigned to cluster 3 that was largely associated with low values of textural FET-PET features. By comparison, tumor-to-normal brain ratio (TNRmax) at the optimal cutoff 2.1 was less predictive of PSP (negative predictive value 57% for detecting true progression, p=0.07 vs. 75% with cluster 3, p=0.04).Principal ConclusionsClustering based on textural O-(2-[18F]fluoroethyl)-L-tyrosine PET features may provide valuable information in assessing the elusive phenomenon of pseudoprogression.

Static FET–PET and MR Imaging in Anaplastic Gliomas (WHO III)

O-(2-[18F]-fluoroethyl)-L-tyrosine-positron emission tomography (FET-PET) imaging is an additional tool for tumor grading and surgery planning. Up to now, not much is known about FET-PET imaging in anaplastic gliomas. Our objective was to assess the FET uptake in anaplastic gliomas, compared with magnetic resonance imaging (MRI), histopathologic markers, and its prognostic value. Forty-six patients (27 males/19 females) with an anaplastic glioma (WHO III) who received MRI and FET-PET imaging before surgery were retrospectively analyzed. Tumor volume was calculated in MRI and FET-PET imaging using a tumor-to-background ratio (TBR), and maximum FET uptake (TBRmax) was calculated. Overall survival (OS) and histopathologic markers (isocitrate-dehydrogenase 1/2-mutation, oligodendrial differentiation, and Ki67 proliferation index) were assessed. Univariate and multivariate analysis was performed for OS. In univariate analysis a significant correlation of TBRmax to OS was observed (P= 0.031). Tumor volume in FET-PET imaging (TBR > 2.0) (P= 0.028) showed a higher correlation to OS than the volume of the contrast-enhancing tumor part (P= 0.031). The highest correlation was observed for intersection of volume TBR > 1.3 and the volume of the contrast-enhancing tumor part (P= 0.005); fluid-attenuated inversion recovery volume showed no significant correlation to OS (P= 0.401) in the univariate analysis. Anaplastic glioma with oligodendrial differentiation showed significantly higher TBRmax values (P= 0.029), while no significant difference was observed for isocitrate hydrogenase 1/2-mutation (P= 0.752). Static FET-PET provides significant prognostic information in anaplastic gliomas, which adds to the value of MRI, supporting the use of both modalities preoperatively to assess individual risks and estimate prognosis. Definition of the histopathologic subtype using static FET-PET remains challenging.

SURG-13THE IMPACT OF MULTIMODAL FUNCTIONAL AND METABOLIC IMAGING OF HIGHLY-ELOQUENT BRAIN TUMORS ON FUNCTIONAL OUTCOME AND EXTENT OF RESECTION

SURG-13. THE IMPACT OF MULTIMODAL FUNCTIONAL AND METABOLIC IMAGING OF HIGHLY-ELOQUENT BRAIN TUMORS ON FUNCTIONAL OUTCOME AND EXTENT OF RESECTION Andrea Faymonville1, Catharina Schroter1, Gabriele Stoffels2, Christian Grefkes2,3, Roland Goldbrunner1, and Carolin Wei Lucas1; Department of Neurosurgery, University of Cologne, Cologne, Germany; Institute of Neuroscience and Medicine, Research Center Juelich, Juelich, Germany; Department of Neurology, University of Cologne, Cologne, Germany INTRODUCTION: Since functional outcome and extent of resection are of crucial importance for the adjuvant treatment and quality of life of patients with eloquently located gliomas, preoperative metabolic and functional imaging helps to delineate metabolically active and functionally relevant tumor parts. Here, the impact of multimodal preoperative imaging on functional outcome and extent of resection was prospectively investigated. METHODS: 54 patients with high grade gliomas (IV8: N 1⁄4 46; III8: N 1⁄4 8) adjacent to the primary motor cortex or the pyramidal tract were allocated to threegroups for matchedpair analysis.GroupM (“multimodal”)was investigated by navigated transcranial magnetic stimulation (nTMS), functional MRI, DTI tractography and O-(2-[18F]Fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) prior to surgery. Group T (“nTMS”) received preoperative nTMS and FET-PET while patients of group S (“standard”) were operated based on contrast-enhanced MRI. Intraoperatively, fluorescence-guidance (5-aminolevolinic acid), neuronavigation and direct cortical stimulation were applied in all groups. Motor function was assessed before surgery and at discharge. Any residual contrast enhancement in the postoperative MRI scan (0-48 hrs. after surgery) was regarded as tumor residual. RESULTS: 52% of the patients had preoperative motor deficits. At discharge, the paresis had improved in 26%, worsened in 7% and remained unchanged in 63%. Tumor size, localization and hemispheric dominance were even in all groups. Distance of tumor to the primary motor cortex/ pyramidal tract was significantly shorter in groups M/T compared to group S. Functional outcome was not significantly different between groups. The rate of complete resections was higher in groups M/T. Moreover, the predictability of the resection extent by the surgeons was significantly higher in those groups. CONCLUSION: Preoperative metabolic and functional imaging of motor-eloquent gliomas improves the resection rates and enables a significantly higher predictability of the resection extent. Moreover, good functional outcome can be achieved whilst operating closer to primary motor areas. Neuro-Oncology 17:v214–v220, 2015. doi:10.1093/neuonc/nov235.13 Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2015.

Volumetric Analysis of F-18-FET-PET Imaging for Brain Metastases

The knowledge of exact tumor margins is of importance for the treating neurosurgeon, radiotherapist, and oncologist alike. The aim of this study was to investigate whether tumor volume and tumor margins acquired by magnetic resonance imaging (MRI) are congruent with the findings acquired by O-(2-(18F)-fluoroethyl)-L-tyrosine-positron emission tomography (FET-PET). Patients received FET-PET and MRI before surgery for brain metastases. Metastases were quantified by calculating tumor-to-background uptake ratios using FET uptake. PET and MRI-based tumor volumes, as well as areas of intersection, were assessed. Forty-one patients were enrolled in the study. The maximum tumor-to-background uptake ratio measured in all of our patients harboring histologically proven viable tumor tissue was >1.6. Absolute tumor volumes acquired by FET-PET and MRI were not congruent in our patient cohort, and tumors identified in FET-PET and MRI only partially overlapped. The ratio of intersection (intersection of tumor defined by MRI and tumor defined by FET-PET at the ratio of tumor defined by FET-PET) was within a range of 0.27-0.68 when applying the different thresholds. Our study therefore indicates that treatment planning based on MRI or PET only might have a substantial risk of undertreatment at the tumor margins. These findings could have important implications for the planning of surgery as well as radiotherapy, although they have to be validated in further studies.

O-(2-[18F]fluoroethyl)-l-tyrosine uptake is an independent prognostic determinant in patients with glioma referred for radiation therapy

To evaluate the prognostic value of O-(2-[(18)F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) uptake intensity in World Health Organisation (WHO) tumor grade II-IV gliomas. We studied 28 patients with WHO tumor grade II-IV gliomas who were referred to our department for radiation therapy. We acquired a FET-PET in all patients, as well as magnetic resonance imaging (MRI) of the brain consisting of at least T2-weighted imaging, flair and pre- and post-contrast T1-weighted imaging. SUVmax was measured and the tumor-to-brain uptake ratio (TBR) of all lesions was calculated based on the SUVmax (TBRmax) or SUVmean (TBRmean) of the contralateral healthy tissue. For this study, volumes were calculated using MRI alone, MRI + the volume with a SUVmax on FET-PET ≥ 2.2 as well as MRI + the volume with an uptake of at least 40 % of the SUVmax. Tumor volumes were a median (range) of 88.6 (2.6-467.4) ml (MRI alone), 84.2 (2.8-474.4) ml (MRI + SUVmax on FET-PET ≥ 2.2) and 101.5 (4.0-512.1) ml (MRI + FET-PET uptake ≥ 40 % SUVmax), respectively. TBR-SUVmean was 2.36 (1.46-4.08); TBR-SUVmax was 1.71 (0.97-2.85). During a follow-up of 18.7 (2.5-36.1) months after FET-PET, 12 patients died of malignant glioma. Patients with a SUVmax ≥ 2.6 had a significantly worse tumor-related mortality (p = 0.005) and progression-free survival (p = 0.038) than those with a lower SUVmax. Multivariate analysis showed that WHO tumor grade (p = 0.001) and SUVmax ≥ 2.6 (p < 0.001) were independent predictors for tumor-related mortality, but not tumor volume or TBRmax or TBRmean. SUVmax ≥ 2.6 (p = 0.007) and being treated for a recurrence rather than for a primary tumor manifestation (p = 0.014) were predictors for progression-free survival, but not TBRmax or TBRmean. In this heterogeneous patient population, higher tracer uptake in FET-PET appears to be associated with a worse tumor-related mortality and a shorter duration of the disease-free interval.

Patients with recurrent glioblastoma multiforme

SummaryAim: The objective of this study was to assess the feasibility, dosimetry, tolerability and efficacy of systemically administrated p-[131I] - iodo-L-phenylalanine (131IPA) combined with hypo-fractionated external beam radiation therapy (EBRT) in patients with recurrent glioblastoma multiforme (GBM). Patients, methods: Five patients (2 women, 3 men, aged 27-69) with recurrent GBM and exhaustion of regular therapy options were included. All had a positive O-(2-[18F]Fluoroethyl)- L-tyrosine positron emission tomography (FET-PET) and pretherapeutic dosimetry was performed. Tumour targeting was verified by 131IPA-SPECT up to six days after radiotracer administration. After 131IPA therapy, patients were treated with hypo-fractionated EBRT in six fractions of 5 Gy (n = 4) or in eleven fractions of 2 Gy in one case. Results: Based on the individual dosimetry, the patients received a single intravenous administration of 2 to 7 GBq of 131IPA, resulting in radiation absorbed doses to the blood of 0.80–1.47 Gy. The treatment was well tolerated; only minor complaints of nausea and vomiting that responded to ondansetron and pantoprazol were noticed in the first two patients. After preventive medication, the last three patients had no complaints during therapy. In none of the patients a decrease of leukocyte or thrombocyte counts below the baseline level or the lower normal limit was observed. Tumour doses from 131IPA were low (≤ 1 Gy) and all patients died three to eight (median 5.5) months after therapy. Conclusion: In this initial experience, treatment of GBM with 131IPA in combination with EBRT was demonstrated to be safe and well tolerated, but less effective than suggested by the animal studies.

Comparative PET study using F-18 FET and F-18 FDG for the evaluation of patients with suspected brain tumour

The aim of this prospective pilot study in patients with suspected or known brain tumour was to establish the diagnostic value of O-(2-[ 18F]-fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) when compared to fluorine-18 fluorodeoxyglucose (FDG) PET. Twenty-five FET PET and FDG PET scans were performed on 21 consecutive patients within 24 months. Final malignant pathology included 11 glioma (eight low-grade, three high grade), two lymphoma, one olfactory ganglioneuroblastoma, one anaplastic meningioma. Benign pathology included two encephalitis and one cortical dysplasia. Definitive pathology was not available in three patients. The accuracy of PET was determined by subsequent surgical histopathology in 12 and clinical/imaging course in nine patients. Median follow-up period was 20 months. FET sensitivity was 93%, specificity 100%, accuracy 96%, positive predictive value (PPV) 100% and negative predictive value (NPV) 91%. FDG sensitivity was 27%, specificity 90%, accuracy 52%, PPV 80% and NPV 45%. FET PET is more accurate than FDG PET for detecting malignant brain lesions, especially low-grade gliomas.

O-(2-[18F]Fluorethyl)-L-Tyrosin (FET) in der Diagnostik von Hirntumoren

Positron emission tomography (PET) using radiolabeled amino acids has shown great potential for a more accurate diagnosis of cerebral gliomas. Magnetic resonance imaging (MRI) is the investigation of choice for diagnosing cerebral glioma, but its capacity to differentiate tumor tissue from non-specific tissue changes is limited. ([ 18 F] Fluoroethyl)-L-tyrosine (FET) is a new tracer for PET that can be produced with high efficiency and distributed on a wide clinical scale like [ 18 F]-Fluorodeoxyglucose (FDG). The use of FET PET allows better delineation of tumor margins and improves targeting of biopsy and radiotherapy, and planning surgery. In addition, amino acid imaging appears useful in distinguishing tumor recurrence from non-specific post-therapeutic scar tissue, predicting prognosis in low grade gliomas, and monitoring metabolic response during treatment.

Verbesserte Diagnostik von zerebralen Gliomen mit der FET PET

Positron emission tomography (PET) using radiolabeled amino acids has shown great potential for more accurate diagnostics of cerebral gliomas. O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) is a new tracer for PET which can be produced with high efficiency and distributed on a wide clinical scale in Germany. In a biopsy-controlled study, a significant improvement of the detection of true tumor extent of cerebral gliomas could be demonstrated by the combined use of FET PET and MRT in comparison with MRT alone. Advantages of FET PET are an improved guidance of biopsies, an improved planning of surgery and radiation therapy, and the differentiation of tumor recurrence from unspecific post-therapeutic tissue changes. Furthermore, FET PET appears to be particularly valuable in the prognosis of low-grade gliomas.

O-(2-[18F]fluoroethyl)-l-tyrosine PET for monitoring the effects of convection-enhanced delivery of paclitaxel in patients with recurrent glioblastoma

Convection-enhanced delivery (CED) of paclitaxel is a new locoregional approach for patients with recurrent glioblastoma. The aim of this study was to evaluate O-(2-[(18)F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) in monitoring the effects of this type of direct drug delivery. Eight patients with recurrent glioblastoma underwent CED of paclitaxel, which was infused over stereotactically placed catheters into the tumour. FET PET and MRI were performed before and 4 weeks after therapy and then at 3-month intervals to document follow-up. For quantitative evaluation, SUV(max)(tumour)/SUV(mean)(background) ratios were calculated. At baseline all tumours showed gadolinium enhancement and high FET uptake (SUV(max)/BG 3.2+/-0.8). Four weeks after CED, a statistically significant decrease in FET uptake was seen (SUV(max)/BG-17%; p<0.01). During follow-up, no recurrence was observed within the CED area. Two out of eight patients with extended tumours died 4 and 5 months after treatment, most probably from local complications. Temporarily stable disease with stable FET uptake was observed in six of eight patients; this was followed by progression and increasing FET uptake ratios (+46%) distant from the CED area in five of the six patients 3-13 months after CED. One patient still presents stable FET uptake 10 months after CED. MRI showed unchanged/increasing contrast enhancement and oedema without ability to reliably assess disease progression. FET PET is a valuable tool in monitoring the effects of CED of paclitaxel. In long-term follow-up, stable or decreasing FET uptake, even in contrast-enhancing lesions, is suggestive of reactive changes, whereas increasing ratios appear always to be indicative of recurrence. Therefore, FET PET is more reliable than MRI in differentiating stable disease from tumour regrowth.

Synthesis and evaluation of O-(3-[ 18F]fluoropropyl)-L-tyrosine as an oncologic PET tracer

O-(3-[ 18F]fluoropropyl)-L-tyrosine (FPT), an analogue of O-(2-[ 18F]fluoroethyl)-L-tyrosine (FET) as an amino acid tracer for tumor imaging with positron emission tomography (PET), was synthesized and evaluated. FPT was prepared by [ 18F]fluoropropylation of L-tyrosine in a two-step procedure. Biodistribution of FPT was determined in normal mice. FPT, FET and [ 18F]fluorine-2-deoxy-D-glucose (FDG) uptake studies were performed in mice bearing S18 fibrosarcoma and S. aureus-inoculated mice. Also, carcinoma-bearing mice and S. aureus-inoculated mice were imaged using FPT PET imaging compared with FET and FDG PET imaging. Synthesis of FPT was accompished in about 60 min with an overall radiochemical yield of 25-30% (without decay correction) by manual operation. High uptake and long retention time of FPT and FET in kidney, liver, lung, blood, etc., and low uptake in brain were found. Furthermore, high FPT, FET and FDG uptake in tumor, and almost no FPT and FET uptake in inflammatory tissue, in contrast, high FDG uptake in inflammatory tissue, were observed. In conclusion, FPT is easy to prepare and superior to FDG in the differentiation of tumor and inflammation, and seems to be a potential amino acid tracer like FET for tumors imaging with PET.