Amino Acid Tracer Research Articles

Beta-hydroxy-beta-methylbutyrate (HMB) improves daily activity and whole-body protein metabolism in Duchenne muscular dystrophy dogs: a pilot study

Duchenne muscular dystrophy (DMD) is a severe neuromuscular disease due to loss of dystrophin, leading to progressive muscle wasting and physical inactivity. In this pilot study, we studied the effect of daily supplementation of the anabolic substrate beta-hydroxy-beta-methylbutyrate (HMB) on whole body protein and amino acid kinetics using novel isotope methods and daily activity in a canine model of DMD. Six DMD dogs were administered 3 g daily of HMB or placebo for 28 days according to a randomized, placebo-controlled, double-blinded crossover design. We measured pre- and post-intervention daily activity, biochemistry markers, and whole-body amino acid kinetics. We tracked daily activity with an activity monitoring device and measured plasma creatine kinase and standard clinical biochemistry panels to monitor muscle and organ function. To calculate whole body and intracellular amino acid production, we administered in the postabsorptive state an IV stable isotope solution containing 20 amino acid tracers. We collected blood before and six times after until two hours post tracer pulse administration and measured amino acid enrichments and concentrations by LC–MS/MS, subsequently followed by (non) compartmental modeling of the decay enrichment curves. Results were expressed as mean with 95% CI. Whole body production, plasma concentrations, and intra-/extracellular compartmental analyses of various amino acids were attenuated in HMB-dosed DMD dogs. Specifically, the plasma concentration of hydroxyproline (marker of collagen breakdown) was significantly higher in the placebo group compared to the HMB group. The intra- and extracellular pool sizes and flux between the two compartments of hydroxyproline was reduced in HMB treated dogs. DMD dogs treated with HMB as compared to placebo had a respective 40% increase in exertional (play) (951 [827, 1075] versus 569 [491, 647]; p < 0.0001) and 10.5% increase in non-exertional (active) activity (15,366 [14742, 15990] versus 13,806 [13148,14466]; p = 0.0016). In addition, a 6% reduction was found in rest time after HMB supplementation compared to placebo (23,857 [23,130, 24,584], versus 25,363 [24500, 26225]; p = 0.0122). Creatine kinase was not statistically different between groups. We did not observe any adverse clinical or biochemical-related effects of HMB dosing. Daily HMB supplementation in DMD dogs can safely and positively influence protein and amino acid metabolism and improve overall daily activity.

BIOM-44.18F-DOPA-PET THRESHOLDS FOR BOTH NEWLY DIAGNOSED AND RECURRENT ASTROCYTOMA USING PATHOLOGICAL GROUPING OF SPATIALLY CORRELATED BIOPSIES

Abstract BACKGROUND Glioma radiotherapy planning requires accurate tumor delineation. While T1- contrast-enhanced-MRI (T1-CE-MRI) is the standard, due to blood-brain-barrier breakdown dependencies, T1-CE-MRI fails to reflect the extent of glioma. Studies using amino acid PET tracers report glioma uptake up to 3cm-4cm beyond T1-CE. In this study, amino acid tracer 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) uptake was correlated with histopathological features to determine tumor thresholds. METHODS Using registered 18F-DOPA-PET and T1-CE-MRI images in the Stealth Neuronavigation system targeting concordant and discordant regions, 181 stereotactic biopsy samples (newly-diagnosed=74; recurrent=107) were obtained from 59 enrolled astrocytoma patients across two prospective phase II clinical trials between 2010-2019. An experienced neuropathologist reviewed each sample with hematoxylin and eosin stain and assigned an alphanumeric score: mitotic activity (0=no tumor; 1=no mitosis; 2=few/scattered mitosis; 3=frequent mitosis) and cellular density (A=&amp;lt;25%; B=25%-50%; C=50%-75%; D=&amp;gt;75%). Samples assigned 1C-1D, 2B-2D, or 3A-3D were categorized as histopathological high-score (aggressive disease), remaining samples as low-score. Relative mean (rFDOPA_mean) tumor-to-background uptake ratios were computed for 5mm uniformly expanded volumes from each Stealth biopsy coordinate using the crescent and wedge normalization methods. Relative uptake was compared overall and separately within newly-diagnosed/recurrent disease subgroups. An optimal rFDOPA_mean threshold to delineate high- from low-score was determined using the maximal Youden index of ROC curves. RESULTS Overall, high-score samples (n=116) had higher median (IQR) rFDOPA_mean uptake than low-score samples (n=65): high-score rFDOPA:mean=1.70(1.16-2.26), low-score rFDOPA:mean=1.16(0.83-1.49), Kruskal-Wallis p&amp;lt;0.001. The uptake difference between high- vs. low-score samples was observed within newly-diagnosed and recurrent subgroups, but was only significant for newly-diagnosed (p&amp;lt;0.001). For newly-diagnosed, an rFDOPA:mean=1.49 cutoff between high- and low-score groups shows 69% accuracy, 63% sensitivity, 80% specificity (AUC=0.782). Using the wedge normalization method, rFDOPA_mean values were 0.2 higher than crescent method values. CONCLUSIONS This work presents histologically verified 18F-DOPA-PET thresholds for aggressive disease in newly-diagnosed astrocytoma patients. Separate thresholds will need to be determined for recurrent glioma patients.

Metabolic kinetics and muscle and brain health markers in older adults, and the role of age and presence of chronic morbidities: A large cross-sectional cohort study

Background & aimsOlder adults are at risk for muscle and cognitive function decline during advanced aging, but the underlying metabolic mechanisms and the role of aging-associated chronic morbidities remain unclear. In the present study, we examined whether protein and amino acid kinetics in older adults with and without chronic morbidities are different when 50-70 and 70-90 of age and related to markers of muscle and brain health declines. MethodsIn a large cross-sectional observational study, 575 older adults from 12 trials (2014-2022) were stratified based on their age (50-70y vs. 70-95y) and the presence of chronic morbidities. The main outcomes were whole-body production (WBP) and interconversions of amino acids by stable amino acid tracers, body composition, and muscle and cognitive performance. Additionally, the association between metabolic markers and muscle and brain health was assessed. ResultsOverall lower muscle strength, muscle and fat mass, and cognitive function (p<0.03), but no mood disturbances, were found in 70-95y compared to 50-70y older adults. Presence of morbidities was associated with lower muscle strength and mass, and cognitive function, but higher visceral adipose tissue, and mood disturbances (p<0.05). Aging was associated with suppressed WBP of most amino acids, de novo arginine production, and net protein breakdown, but higher myofibrillar protein breakdown (p<0.007). Presence of morbidities was associated with lower WBP of glutamine, glutamate, histidine, isoleucine, phenylalanine, tyrosine, and net protein breakdown, and higher WBP of valine and taurine (p<0.04). Age showed significant negative correlations with WBP of nearly all amino acids, de novo arginine production and net protein breakdown (r: [-0.407, -0.136], p<0.01) but a positive correlation with WBP of myofibrillar protein breakdown (r=0.133, p=0.009). Lean mass showed positive correlations with de novo arginine production and net protein breakdown and WBP of all amino acids except for isoleucine (r: [0.16, 0.799], p<0.005). Worse cognitive performance was positively associated with WBP of tau-methylhistidine and taurine (r: [0.13, 0.141], p<0.04), but negatively associated with WBP of glycine, valine, and net protein breakdown (r: [-0.222, -0.135], p<0.05). ConclusionComprehensive phenotyping of a large group of older adults revealed differences in metabolic health in response to advanced aging and chronic morbidities. Poor muscle health accompanied by advanced aging was associated with overall metabolic downregulation, except for enhanced myofibrillar (muscle) protein breakdown. Presence of chronic morbidities was further associated with disturbed muscle health, mood, arginine, and taurine pathways, and higher visceral adipose tissue. Therefore, different phenotypes among older adults need to be considered when evaluating therapeutic approaches to improve muscle and brain health.

Advanced imaging techniques and non-invasive biomarkers in pediatric brain tumors: state of the art.

In the pediatric age group, brain neoplasms are the second most common tumor category after leukemia, with an annual incidence of 6.13 per 100,000. Conventional MRI sequences, complemented by CT whenever necessary, are fundamental for the initial diagnosis and surgical planning as well as for post-operative evaluations, assessment of response to treatment, and surveillance; however, they have limitations, especially concerning histopathologic or biomolecular phenotyping and grading. In recent years, several advanced MRI sequences, including diffusion-weighted imaging, diffusion tensor imaging, arterial spin labelling (ASL) perfusion, and MR spectroscopy, have emerged as a powerful aid to diagnosis as well as prognostication; furthermore, other techniques such as diffusion kurtosis, amide proton transfer imaging, and MR elastography are being translated from the research environment to clinical practice. Molecular imaging, especially PET with amino-acid tracers, complement MRI in several aspects, including biopsy targeting and outcome prediction. Finally, radiomics with radiogenomics are opening entirely new perspectives for a quantitative approach aiming at identifying biomarkers that can be used for personalized, precision management strategies.

Value of 11C-Methionine PET Imaging in High-Grade Gliomas: A Narrative Review.

11C-Methionine (MET) is a widely utilized amino acid tracer in positron emission tomography (PET) imaging of primary brain tumors. 11C-MET PET offers valuable insights for tumor classification, facilitates treatment planning, and aids in monitoring therapeutic response. Its tracer properties allow better delineation of the active tumor volume, even in regions that show no contrast enhancement on conventional magnetic resonance imaging (MRI). This review focuses on the role of MET-PET in brain glioma imaging. The introduction provides a brief clinical overview of the problems of high-grade and recurrent gliomas. It discusses glioma management, radiotherapy planning, and the difficulties of imaging after chemoradiotherapy (pseudoprogression or radionecrosis). The mechanism of MET-PET is described. Additionally, the review encompasses the application of MET-PET in the context of primary gliomas, addressing its diagnostic precision, utility in tumor classification, prognostic value, and role in guiding biopsy procedures and radiotherapy planning.

PET imaging of gliomas: Status quo and quo vadis?

PET imaging, particularly using amino acid tracers, has become a valuable adjunct to anatomical MRI in the clinical management of patients with glioma. Collaborative international efforts have led to the development of clinical and technical guidelines for PET imaging in gliomas. The increasing readiness of statutory health insurance agencies, especially in European countries, to reimburse amino acid PET underscores its growing importance in clinical practice. Integrating artificial intelligence and radiomics in PET imaging of patients with glioma may significantly improve tumor detection, segmentation, and response assessment. Efforts are ongoing to facilitate the clinical translation of these techniques. Considerable progress in computer technology developments (eg quantum computers) may be helpful to accelerate these efforts. Next-generation PET scanners, such as long-axial field-of-view PET/CT scanners, have improved image quality and body coverage and therefore expanded the spectrum of indications for PET imaging in Neuro-Oncology (eg PET imaging of the whole spine). Encouraging results of clinical trials in patients with glioma have prompted the development of PET tracers directing therapeutically relevant targets (eg the mutant isocitrate dehydrogenase) for novel anticancer agents in gliomas to improve response assessment. In addition, the success of theranostics for the treatment of extracranial neoplasms such as neuroendocrine tumors and prostate cancer has currently prompted efforts to translate this approach to patients with glioma. These advancements highlight the evolving role of PET imaging in Neuro-Oncology, offering insights into tumor biology and treatment response, thereby informing personalized patient care. Nevertheless, these innovations warrant further validation in the near future.

IMG-19. CLINICAL UTILITY OF NON-FDG PET-MRI IN CHILDREN WITH CNS NEOPLASMS: A TERRITORY-WIDE STUDY FROM HONG KONG

Abstract INTRODUCTION Magnetic resonance imaging (MRI) is the gold-standard for neuroimaging, yet details from anatomical scans might be inconclusive in certain scenarios. This study aimed to investigate the utility of amino-acid tracer positron emission tomography-magnetic resonance imaging (PET-MRI) based on a territory-wide Pediatric Neuro-Oncology cohort from Hong Kong. METHODS We reviewed the PET-MRI scans of pediatric patients with suspected/confirmed CNS neoplasms co-managed by Hong Kong Children’s Hospital and St. Teresa’s Hospital, Hong Kong from 5/2022-1/2024. Tracers used included C11-MET (n=10, before 5/2023) and F18-FET (n=15, in/after 5/2023). Lesion-to-normal SUVmax ratios (LNRmax) were measured with reference to adjacent or contralateral normal brain structures. RESULTS Twenty-five patients were included (M:F=13:12) with a median age of 10 years (range: 1-17). Anatomical sites of interest were the pituitary (n=13), basal ganglia (n=3), cerebellum (n=3), brainstem (n=2), frontal lobe (n=2), cerebellopontine angle (n=1), and spine (n=1). PET-MRI was performed as part of initial diagnostics in 21, to assess post-operative residual in 2, and for possible relapse in 2. Among those evaluated upfront (n=21), median SUVmax and LNRmax were 1.53 (range: 0.87-2.6) and 0.87 (range: 0.45-1.92) respectively in patients with presumed/confirmed low-grade glioneuronal (n=5) or non-oncologic lesions (n=8), versus 4.75 (range: 2.58-9.6) and 3.26 (range: 1.78-4.9) in patients with histologically/biochemically confirmed high-grade lesions (germinoma=6, high-grade glioma=2). Availability of functional PET imaging was deemed useful for scan interpretation in all 25 patients. Specifically, the use of PET-MRI facilitated decision for radiographic surveillance without biopsy/resection in 12 patients, refined tumor grading in 2 patients with discrepant clinical-histologic features, and allowed response-adapted therapy after serial scans in 5 patients. CONCLUSIONS Our study demonstrates the potential benefits of PET-MRI in the management of children with CNS pathologies. PET-MRI contributes to the diagnosis, monitoring, and treatment guidance of these patients, providing crucial information for clinical decision-making.

Quantification and interpretation of postprandial whole-body protein metabolism using stable isotope methodology: a narrative review.

Stable isotopes are routinely applied to determine the impact of factors such as aging, disease, exercise, and feeding on whole-body protein metabolism. The most common approaches to quantify whole-body protein synthesis, breakdown, and oxidation rates and net protein balance are based on the quantification of plasma amino acid kinetics. In the postabsorptive state, plasma amino acid kinetics can easily be assessed using a constant infusion of one or more stable isotope labeled amino acid tracers. In the postprandial state, there is an exogenous, dietary protein-derived amino acid flux that needs to be accounted for. To accurately quantify both endogenous as well as exogenous (protein-derived) amino acid release in the circulation, the continuous tracer infusion method should be accompanied by the ingestion of intrinsically labeled protein. However, the production of labeled protein is too expensive and labor intensive for use in more routine research studies. Alternative approaches have either assumed that 100% of exogenous amino acids are released in the circulation or applied an estimated percentage based on protein digestibility. However, such estimations can introduce large artifacts in the assessment of whole-body protein metabolism. The preferred estimation approach is based on the extrapolation of intrinsically labeled protein-derived plasma bioavailability data obtained in a similar experimental design setting. Here, we provide reference data on exogenous plasma amino acid release that can be applied to allow a more accurate routine assessment of postprandial protein metabolism. More work in this area is needed to provide a more extensive reference data set.

Post-prandial tracer studies of protein and amino acid utilisation: what can they tell us about human amino acid and protein requirements?

Nitrogen balance (NB), the principal methodology used to derive recommendations for human protein and amino acid requirements, has been widely criticised, and calls for increased protein and amino acid requirement recommendations have been made, often on the basis of post-prandial amino acid tracer kinetic studies of muscle protein synthesis, or of amino acid oxidation. This narrative review considers our knowledge of the homeostatic regulation of the FFM throughout the diurnal cycle of feeding and fasting and what can and has been learnt from post-prandial amino acid tracer studies, about amino acid and protein requirements. Within the FFM, muscle mass in well fed weight-stable adults with healthy lifestyles appears fixed at a phenotypic level within a wide range of habitual protein intakes. However homoeostatic regulation occurs in response to variation in habitual protein intake, with adaptive changes in amino acid oxidation which influence the magnitude of diurnal losses and gains of body protein. Post-prandial indicator amino acid oxidation (IAAO) studies have been introduced as an alternative to NB and to the logistically complex 24 h [13C-1] amino acid balance studies, for assessment of protein and amino acid requirements. However, a detailed examination of IAAO studies shows both a lack of concern for homeostatic regulation of amino acid oxidation and major flaws in their design and analytical interpretation, which seriously constrain their ability to provide reliable values. New ideas and a much more critical approach to existing work is needed if real progress is to be made in the area.

Ammonification by kelp associated microbes increases ammonium availability.

Microbes contribute biologically available nitrogen to the ocean by fixing nitrogen gas from the atmosphere and by mineralizing organic nitrogen into bioavailable dissolved inorganic nitrogen (DIN). Although the large concentration of plants and algae in marine coastal environments provides ample habitat and reliable resources for microbial communities, the role of the microbiome in host-microbe nitrogen cycling remains poorly understood. We tested whether ammonification by epiphytic microbes increased water column ammonium and improved host access to nitrogen resources by converting organic nitrogen into inorganic nitrogen that is available for assimilation by hosts. When bull kelp (Nereocystis luetkeana) in the northeast Pacific was incubated with 15N labelled amino acid tracers, there was accumulation of 15N in kelp tissue, as well as accumulation of 15NH4 in seawater, all consistent with the conversion of dissolved organic nitrogen to ammonium. Metagenomic analysis of surface microbes from two populations of Nereocystis indicated relative similarity in the percentage of genes related to ammonification between the two locations, though the stressed kelp population that had lower tissue nitrogen and a sparser microbiome had greater ammonification rates. Microbial communities on coastal macrophytes may contribute to the nitrogen requirements of their hosts through metabolisms that make ammonium available.

Molecular Imaging of Glial Tumors: Established and Emerging Tracers

AbstractVarious positron emission tomography (PET) tracers have been developed and extensively studied in the field of neuro-oncology imaging. In the management of brain tumors, accurate delineation of tumor extent, assessment of treatment response, and detection of early recurrence are the most important factors. At present, conventional anatomical imaging paired with amino acid tracer PET imaging is the recommended imaging modality for glial tumor evaluation. Newer PET tracers targeting various structures in the tumor microenvironment have been extensively studied. This review summarizes the established and emerging PET tracers having potential impact on neuro-oncology practice.

Skeletal muscle protein turnover responses to parenteral nutrition in patients with alcoholic liver cirrhosis and sarcopenia.

Alcoholic liver cirrhosis (ALC) is accompanied by sarcopenia. The aim of this study was to investigate the acute effects of balanced parenteral nutrition (PN) on skeletal muscle protein turnover in ALC. Eight male patients with ALC and seven age- and sex-matched healthy controls were studied for 3 h of fasting followed by 3 h of intravenous PN (SmofKabiven 1,206 mL: amino acid = 38 g, carbohydrates = 85 g, and fat = 34 g) 4 mL/kg/h. We measured leg blood flow and sampled paired femoral arteriovenous concentrations and quadriceps muscle biopsies while providing a primed continuous infusion of [ring-2d5]-phenylalanine to quantify muscle protein synthesis and breakdown. Patients with ALC exhibited shorter 6-min walking distance (ALC: 487 ± 38 vs. controls: 722 ± 14 m, P < 0.05), lower hand-grip strength (ALC: 34 ± 2 vs. controls: 52 ± 2 kg, P < 0.05), and computed tomography (CT)-verified leg muscle loss (ALC: 5,922 ± 246 vs. controls: 8,110 ± 345 mm2, P < 0.05). Net leg muscle phenylalanine uptake changed from negative (muscle loss) during fasting to positive (muscle gain) in response to PN (ALC: -0.18 ± +0.01 vs. 0.24 ± 0.03 µmol/kg muscle·min-1; P < 0.001 and controls: -0.15 ± 0.01 vs. 0.09 ± 0.01 µmol/kg muscle·min-1; P < 0.001) but with higher net muscle phenylalanine uptake in ALC than controls (P < 0.001). Insulin concentrations were substantially higher in patients with ALC during PN. Our results suggest a higher net muscle phenylalanine uptake during a single infusion of PN in stable patients with ALC with sarcopenia compared with healthy controls.NEW & NOTEWORTHY Muscle protein turnover responses to parenteral nutritional (PN) supplementation have not previously been studied in stable alcoholic liver cirrhosis (ALC). We applied stable isotope tracers of amino acids to directly quantify net muscle protein turnover responses to PN in sarcopenic males with ALC and healthy controls. We found a higher net muscle protein gain in ALC during PN, thereby providing the physiological rationale for future clinical trials of PN as a potential countermeasure to sarcopenia.

The complementary role of MRI and FET PET in high-grade gliomas to differentiate recurrence from radionecrosis.

Conventional magnetic resonance imaging (MRI) has limitations in differentiating tumor recurrence (TR) from radionecrosis (RN) in high-grade gliomas (HGG), which can present with morphologically similar appearances. Multiparametric advanced MR sequences and Positron Emission Tomography (PET) with amino acid tracers can aid in diagnosing tumor metabolism. The role of both modalities on an individual basis and combined performances were investigated in the current study. Patients with HGG with MRI and PET within three weeks were included in the retrospective analysis. The multiparametric MRI included T1-contrast, T2-weighted sequences, perfusion, diffusion, and spectroscopy. MRI was interpreted by a neuroradiologist without using information from PET imaging. 18F-Fluoroethyl-Tyrosine (FET) uptake was calculated from the areas of maximum enhancement/suspicion, which was assessed by a nuclear medicine physician (having access to MRI to determine tumor-to-white matter ratio over a specific region). A definitive diagnosis of TR or RN was made based on the combination of multidisciplinary joint clinic decisions, histopathological examination, and clinic-radiological follow-up as applicable. 62 patients were included in the study between July 2018 and August 2021. The histology during initial diagnosis was glioblastoma, oligodendroglioma, and astrocytoma in 43, 7, and 6 patients, respectively, while in 6, no definitive histological characterization was available. The median time from radiation (RT) was 23 months. 46 and 16 patients had TR and RN recurrence, respectively. Sensitivity, specificity, and accuracy using MRI were 98, 77, and 94%, respectively. Using PET imaging with T/W cut-off of 2.65, sensitivity, specificity, and accuracy were 79, 84, and 80%, respectively. The best results were obtained using both imaging combined with sensitivity, specificity, and accuracy of 98, 100, and 98%, respectively. Combined imaging with MRI and FET-PET offers multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value.

A Review on Brain Tumour, Etiology and Treatment

Brain tumors are common, requiring general medical providers to have a basic understanding of their diagnosis and management. The most prevalent brain tumors are intracranial metastases from systemic cancers, meningiomas, and gliomas, specifically, glioblastoma. Central nervous system metastases may occur anywhere along the neuroaxis, and require complex multidisciplinary care with neurosurgery, radiation oncology, and medical oncology. Meningiomas are tumors of the meninges, mostly benign and often managed by surgical resection, with radiation therapy and chemotherapy reserved for high-risk or refractory disease. Glioblastoma is the most common and aggressive malignant primary brain tumor, with a limited response to standard-of-care concurrent chemoradiation. This review addresses the specific contributions of nuclear medicine techniques, and especially positron emission tomography (PET), for diagnosis and management of brain tumors. F-Fluorodeoxyglucose PET has particular strengths in predicting prognosis and differentiating cerebral lymphoma from nonmalignant lesions. Amino acid tracers including C-methionine, F-fluoroethyltyrosine, and F-L-3,4-dihydroxyphenylalanine provide high sensitivity, which is most useful for detecting recurrent or residual gliomas, including most low-grade gliomas. They also play an increasing role for planning and monitoring of therapy. F-fluorothymidine can only be used in tumors with absent or broken blood–brain barrier and has potential for tumor grading and monitoring of therapy. Ligands for somatostatin receptors are of particular interest in pituitary adenomas and meningiomas. Tracers to image neovascularization, hypoxia, and phospholipid synthesis are under investigation for potential clinical use.

An overview of radiolabeled amino acid tracers in oncologic imaging.

Molecular imaging has witnessed a great progress in the field of oncology over the past few decades. Radiolabeled amino acid (AA) tracers are particularly helpful in the areas where the utility of 18F-Fluorodeoxyglucose (18F-FDG) positron emission tomography with computed tomography imaging has been limited such as in evaluating brain tumors, neuroendocrine tumors (NETs), and prostate cancer. Radiolabeled AA tracers such as 6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-FDOPA), 18F-fluoro-ethyl-tyrosine (18F-FET), and 11C-methionine have found wide applications in brain tumors, which, unlike 18F-FDG, concentrate in the tumor tissue to a greater extent than that in normal brain tissue by providing accurate information about tumor volume and boundaries. 18F-FDOPA is also useful in evaluating NETs. Tracers such as 18F-FACBC (Fluciclovine) and anti-1-amino-2-[18F]fluorocyclopentyl-1-carboxylic acid (18F-FACPC) are used in imaging of prostate cancer and provide valuable information of locoregional, recurrent, and metastatic disease. This review highlights AA tracers and their major applications in imaging, viz., in evaluating brain tumors, NETs, and prostate cancer.

Amino Acid Tracer PET MRI in Glioma Management: What a Neuroradiologist Needs to Know.

PET with amino acid tracers provides additional insight beyond MR imaging into the biology of gliomas that can be used for initial diagnosis, delineation of tumor margins, planning of surgical and radiation therapy, assessment of residual tumor, and evaluation of posttreatment response. Hybrid PET MR imaging allows the simultaneous acquisition of various PET and MR imaging parameters in a single investigation with reduced scanning time and improved anatomic localization. This review aimed to provide neuroradiologists with a concise overview of the various amino acid tracers and a practical understanding of the clinical applications of amino acid PET MR imaging in glioma management. Future perspectives in newer advances, novel radiotracers, radiomics, and cost-effectiveness are also outlined.

The Role of PET Imaging in the Differential Diagnosis between Radiation Necrosis and Recurrent Disease in Irradiated Adult-Type Diffuse Gliomas: A Systematic Review.

Adult-type diffuse gliomas are treated with a multimodality treatment approach that includes radiotherapy both in the primary setting, and in the case of progressive or recurrent disease. Radiation necrosis represents a major complication of radiotherapy. Recurrent disease and treatment-related changes are often indistinguishable using conventional imaging methods. The present systematic review aims at assessing the diagnostic role of PET imaging using different radiopharmaceuticals in differentiating radiation necrosis and disease relapse in irradiated adult-type diffuse gliomas. We conducted a comprehensive literature search using the PubMed/MEDLINE and EMBASE databases for original research studies of interest. In total, 436 articles were assessed for eligibility. Ten original papers, published between 2014 and 2022, were selected. Four articles focused on [18F]FDG, seven on amino acid tracers ([18F]FET n = 3 and [11C]MET n = 4), one on [11C]CHO, and one on [68Ga]Ga-PSMA. Visual assessment, semi-quantitative methods, and radiomics were applied for image analysis. Furthermore, 2/10 papers were comparative studies investigating different radiopharmaceuticals. The present review, the first one on the topic in light of the new 2021 CNS WHO classification, highlighted the usefulness of PET imaging in distinguishing radiation necrosis and tumour recurrence, but revealed high heterogeneity among studies.

NIMG-77. MAGNETIC RESONANCE IMAGING AND AMINO ACID POSITRON EMISSION TOMOGRAPHY IN DIFFERENTIATING TUMOR RECURRENCE FROM RADIATION NECROSIS IN HIGH GRADE GLIOMAS

Abstract BACKGROUND AND PURPOSE Differentiating tumor recurrence (TR) from radiation necrosis (RN) in high grade glioma (HGG) following radiotherapy can be challenging. The ability of conventional magnetic resonance imaging (MRI) to differentiate TR from post-therapeutic effects is often limited. Multiparametric advanced MRI (perfusion) and positron emission tomography (PET) with amino acid tracers, specifically 18F-Fluoroethyl-Tyrosine (FET) can provide relevant additional information on tumor metabolism, which allows for a more accurate diagnosis to differentiate tumor recurrence from radiation necrosis in high grade gliomas. MATERIALS AND METHODS Prospective analysis of 62 lesions in 62 patients with HGG who underwent both MRI and FET-PET imaging within three weeks intervals was done independently by a neuroradiologist and nuclear medicine physician. The study was conducted in a tertiary care oncology center between July 2018 and August 2021. Manually segmented regions of interest were placed over the areas of maximum enhancement/suspicion on MRI and FET uptake, which were used to calculate the relative cerebral volume (rCBV) and tumor to background ratios, respectively. Definitive diagnosis (TR versus RN) was made on clinico-radiological follow-up or histopathological report (wherever available). RESULTS Out of the 62 lesions that were studied, 46 and 16 had TR and RN, respectively. The sensitivity and specificity for determination of TR in HGG with conventional MRI were 98% and 62.5% respectively, while with FET-PET it was 91% and 87.5% respectively. The PPV , NPV and accuracy for MRI were 88%, 91% , 89% , while for FET-PET it was 95%, 78% and 90% respectively. A combination of MRI and PET parameters (mean target-to-background ratio), demonstrated an increase in diagnostic accuracy to 97%. CONCLUSION Cumulative imaging with MRI and FET-PET offers a multiparametric assessment of glioma recurrence that is correlative and complimentary, with higher accuracy and clinical value.

NIMG-28. USE OF NEUROIMAGING TECHNIQUES IN GLIOMA PATIENTS – RESULTS OF AN INTERNATIONAL SURVEY ON BEHALF OF THE EORTC BRAIN TUMOR GROUP

Abstract BACKGROUND Multimodal imaging offers the potential to provide valuable diagnostic information in brain tumor patients. Considering the increasing number and availability of advanced neuroimaging techniques, selecting, and applying the best modality may be therefore difficult. The present survey was carried out to evaluate the preferred use of various neuroimaging applications in patients with glioma. METHODS An online survey with 31 questions was distributed to 262 centers associated with the EORTC located in 34 countries. Subsequently, this survey was promoted by EANO and SNO via social media and newsletters. RESULTS A total of 77 responses, predominantly from radiation oncologists (36%) and neurooncologists (31%), were evaluated. Most responses came from university hospitals and research institutions (68%), mainly from Europe (89%). Almost half of these centers (48%) examined more than 100 glioma patients per year. All institutions had access to MRI, 94% to CT, 67% to PET or PET/CT, and 27% to hybrid PET/MRI. A total of 56% of institutions used RANO criteria for the evaluation of imaging findings. In addition to structural MRI, most institutions routinely performed advanced MRI, followed by CT, PET, and hybrid PET/CT (74%, 42%, 32%, and 23%, respectively). Regarding PET, 64% of centers used the amino acid tracer O-(2-[18F]fluoroethyl)-L-tyrosine, followed by 2-[18F]-fluoro-2-deoxy-D-glucose (45%). Twenty-five percent of centers performed intraoperative MRI, and 10% intraoperative CT. In addition to structural MRI, the preferred additional imaging methods were perfusion-weighted MRI, diffusion-weighted MRI, amino acid PET, and proton MR spectroscopy (83%, 75%, 60% and 56%, respectively). CONCLUSION The results of this international survey provide insights into the use of neuroimaging techniques in neuro-oncology centers. The availability, use, and assessment of neuroimaging in glioma patients varies from country to country. Our results highlight the importance of global activities towards further standardization of neuroimaging in brain tumor patients, such as the RANO working groups.

P15.14.B Radionecrosis versus progression in brain tumors: results of a promising MRI tools

Abstract Background Distinguish between radiation necrosis (RN) and tumor progression, in patients with irradiated primary or metastatic brain tumors, is a diagnostic challenge. Also the use of new MRI sequences, like diffusion, perfusion-weighted and spectroscopy, or PET with new amino acid tracers, is not always able to differentiate these two entities.To overcome this crucial problem, encouraging results have been obtained using the analysis of delayed contrast extravasation MRI to calculate high resolution maps, called “treatment response assessment maps” (TRAMs). Aim of this exploratory analysis is to assess TRAM ability in differentiate between radiation effect and tumor progression in a small cohort of brain tumor patients treated with radiation therapy (RT). Material and Methods Thirty-four patients irradiated for primary and metastatic brain tumors were evaluated. 12 patients have primary brain tumors, 22 patients have brain metastases from different solid tumors. Distinguish by histological subtypes and type of treatment, the 12 patients with primary brain tumors were: 8 glioblastoma, 2 anaplastic astrocitoma, 1 pleomorphic xanthoastrocytoma WHO grade II, and 1 anaplastic xanthoastrocytoma WHO grade III, treated with surgery followed by RT and concomitant and\or adjuvant chemotherapy with temozolomide. Among brain metastatic patients, primary tumor was: 18 non-small cell lung cancer, 2 malignant melanoma, 1 breast cancer and 1 renal cell carcinoma. All of them were treated with stereotactic radiosurgery at the dose of 20-24Gy in 1fraction, or with hypofractionated stereotactic radiotherapy at the dose of 27-30Gy in 3fractions. All images were uploaded and elaborate into the image workstation ([Brainlab AG, Olof-Palme-Straße 9, 81829 Munich]). TRAMs were calculated by subtracting T1 MRI images acquired 5 minutes after contrast injection from the T1 MRI images acquired 60-105 minutes later. On TRAMs, radiation effects appeared as red areas whereas persistent tumoral lesion appeared as blue areas. Results From February 2021, 34 patients have been evaluated, in a prospective study, with this novel MRI modality. During their follow-up, 13patients (38%) showed a clinicoradiologic suspicion of a persistent tumoral lesion or progressive disease, and 21 (62%) a suspicion of RN. For 14patients a brain MET-PET has been performed. TRAMs analysis have shown a fair agreement with clinicoradiologic diagnosis, perfusion-weighted MRI, and PET imaging. Moreover, 7 patients underwent surgical resection, with histopathological confirm of persistent disease in 4 and radionecrosis in 3. Conclusion These preliminary results show the ability of TRAMs evaluation in distinguish between RN and progressive disease. The recruitment of new patients continues, and further evaluations are ongoing to evaluate sensitivity and positive predictive value of TRAMs analysis.