NIMG-18. [18F]FLUCICLOVINE PET TO DISTINGUISH PSEUDOPROGRESSION FROM TUMOR PROGRESSION IN POST-TREATMENT GLIOBLASTOMA

Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of [18F]Fluciclovine PET in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma. METHODS: 23 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement ( > 25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently underwent resection of enhancing lesion and tumor percentage vs. treatment-related changes were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if < 50% and > 10%, and PsP if tumor represented ≤ 10%. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak and SUVmax (g/mL units). RESULTS: 15 patients with “true” TP, 3 with mixed TP-PsP, and 5 with PsP were included. There was a positive correlation between SUVpeak by PET and tumor percentage by histology (Rho= 0.56, p= 0.006). Patients who demonstrated “true” TP had significantly higher SUVpeak compared to patients with histological PsP (4.8±1.6 vs 2.9± 1.0, p= 0.02, AUC= 0.91, n=20). SUVpeak cut-off of 3.3 provided 93% sensitivity, 80% specificity, and 90% accuracy for differentiation of “true” TP from PsP. Patients with “true” TP/mixed TP-PsP also had significantly higher SUVpeak than patients with PsP (4.6±1.5 vs 2.9± 1.0, p= 0.03, AUC= 0.88, n=23). SUVmax and partial volume-corrected SUVpeak and SUVmax exhibited similar performance. CONCLUSION: Our results indicated that [18F]Fluciclovine PET imaging can accurately differentiate “true” TP from PsP. Further studies are required to confirm these promising early results and determine optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from TP.

Systematic Review of the Interaction between Nutrition and Immunity in Livestock: Effect of Dietary Supplementation with Synthetic Amino Acids

Infectious diseases represent one of the most critical threats to animal production worldwide. Due to the rise of pathogen resistance and consumer concern about chemical-free and environmentally friendly productions, the use of antimicrobials drugs is no longer desirable. The close relationship between nutrition and infection has led to numerous studies about livestock. The impact of feeding strategies, including synthetic amino acid supplementation, on host response to various infections has been investigated in different livestock animals. This systematic review provides a synthesis of the experimental studies on the interactions between synthetic amino acid supplementation and immune response to infectious diseases in livestock. Following PRISMA guidelines, quantitative research was conducted using two literature databases, PubMed and Web of Science. The eligibility criteria for the research articles were: (1) the host is a livestock animal; (2) the supplementation with at least one synthetic amino acid; (3) at least one mediator of immunity is measured; (4) at least one production trait is measured. Data were extracted from 58 selected studies. Articles on poultry were the most numerous; few contained experiments using ruminants and pigs. Most of the authors hypothesized that synthetic amino acid supplementation would particularly improve the animals’ immune response against intracellular pathogens. An increase in T and natural killer lymphocytes and macrophages activation, intracellular redox state, lymphocytes proliferation and antibodies production were the most described immune mechanisms associated with synthetic amino acid supplementation. Most of the selected studies focused on three amino acids (methionine, threonine and arginine), all of which are associated with a significant improvement of the host immune response. The use of synthetic amino acid supplementation appears as an encouraging perspective for livestock infectious disease management, and research must concentrate on more analytical studies using these three amino acids.

BIMG-12. [18F]FLUCICLOVINE PET TO DISTINGUISH PSEUDOPROGRESSION FROM TUMOR PROGRESSION IN POST-TREATMENT GLIOBLASTOMA

PURPOSE Differentiation of true tumor progression from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma (GBM). [18F]Fluciclovine is a synthetic amino acid PET radiotracer that is FDA approved in the setting of biochemical recurrence in prostate cancer. The aim of this study was to assess the value of [18F]Fluciclovine PET in differentiation of true tumor progression and PsP in post-treatment of glioblastoma. METHODS 15 patients with GBM with new contrast-enhancing lesions or lesions showing increased enhancement (>25% increase) on standard MRI after completion of radiation underwent 60-minutes dynamic [18F]Fluciclovine PET imaging. Patients subsequently (within 1 week) underwent resection of the enhancing lesion and the tumor percentage vs treatment-related changes were quantified on histopathology. Patients were considered true tumor progression if tumor represented ≥ 50% of the resected specimen and considered PsP if treatment-related changes represented ≥70% of the resected specimen. Summed 30- to 40-minute post-injection PET images were used to measure SUVpeak, SUVmax, and 50% threshold SUVmean. RESULTS 10 patients with true tumor progression and 5 patients with PsP were included. Patients who demonstrated true tumor progression had significantly higher SUVpeak compared to patients with PsP (5.3±1.4 vs 3.1± 0.9, p=0.002, AUC=0.92, p<0.0001). SUVpeak cut-off of 3.5 provided 100% sensitivity, 80% specificity and 93% accuracy for differentiation of true tumor progression from PsP. There was a moderate to strong correlation between SUVpeak and tumor percentage on histopathology (Rho= 0.68, p=0.004). Alternative SUV measures had similar performance. DISCUSSION Our preliminary results indicated that [18F]Fluciclovine PET imaging can accurately differentiate true tumor progression from PsP. Further studies are required to confirm these promising early results and determine the optimal criteria for interpreting [18F]Fluciclovine PET to distinguish PsP from true tumor progression.

Sinorhizobium meliloti Chemotaxis to Multiple Amino Acids Is Mediated by the Chemoreceptor McpU

The legume symbiont Sinorhizobium meliloti is chemoattracted to compounds exuded by germinating seeds of its host alfalfa. This response is mainly mediated by the S. meliloti chemoreceptor McpU. McpU also has a prominent contribution in sensing a synthetic amino acid (aa) mixture mimicking the amounts and composition observed in seed exudate. Here, we used the hydrogel capillary assay to quantify chemotactic responses of S. meliloti to individual aa exuded by germinating alfalfa seeds and to define the role of McpU in this behavior. S. meliloti exhibited positive chemotaxis responses to all proteinogenic aa, except for aspartate, and to citrulline, cystine, gamma-aminobutyric acid, and ornithine. Wild-type responses were diverse in intensity, while a strain lacking mcpU displayed strongly diminished responses. Differential scanning fluorimetry demonstrated interaction of the purified periplasmic region of McpU (McpU-PR) with the aa, except glutamate and aspartate. We additionally tested organic acids and sugars, but there were no significant interactions with the McpU ligand-binding domain, except for citrate. Using ligand displacement, we confirmed the interaction of McpU-PR with aa representing strong and weak attractants. Our results show that S. meliloti McpU is a broad-range aa receptor mediating differential responses to individual attractants, which does not bind negatively charged aa.