Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.

Manufacturing 6-[18F]Fluoro-L-DOPA via Flow Chemistry-Enhanced Photoredox Radiofluorination.

In this study, we introduce a practical methodology for the synthesis of PET probes by seamlessly combining flow chemistry with photoredox radiofluorination. The clinical PET tracer 6-[18F]FDOPA was smoothly prepared in a 24.3% non-decay-corrected yield with over 99.0% radiochemical purity (RCP) and enantiomeric excess (ee), notably by a simple cartridge-based purification. The flow chemistry-enhanced photolabeling method supplies an efficient and versatile solution for the synthesis of 6-[18F]FDOPA and for more PET tracer development.

Adult Neuroblastoma of the Neck Is Better Imaged With 18 F-FDG PET/CT Than With 18 F-DOPA PET/CT.

ABSTRACT: A 41-year-old woman presented with 2 months history of right submandibular swelling. Biopsy revealed neuroblastoma (NB). Patient was referred for staging PET/CT scan. We compared the findings of 18 F-DOPA PET/CT and 18 F-FDG PET/CT scans. Both imaging modalities were positive in the patient; however, tumor delineation was superior with 18 F-FDG PET/CT. Tumor uptake of FDG was significantly higher than tumor uptake of DOPA. Follow-up FDG PET/CT scan postsurgery showed local recurrent NB and their metastases avidly concentrate FDG. We present a very rare case of adult NB of the neck better imaged with FDG instead of DOPA PET/CT.

Chemically Modulating Ceria-Based Artificial Haloperoxidase for Enhanced Antibacterial Activity and Biofilm Inhibition.

Ceria (CeO2) nanoparticles with haloperoxidase (HPO)-like activity have gained attention as a biologically benign antifoulant. 3,4-Dihydroxy-l-phenylalanine (DOPA), a main composition in mussel foot proteins, plays a crucial role in the biofouling process. However, the impact on the HPO-like activity and antifouling performance of CeO2 nanoparticles when DOPA molecules adsorb on them remains unexplored. This interesting question warrants investigation, particularly considering that it may occur in an actual marine environment. Herein, the interaction between DOPA and CeO2 is explored. Despite the higher Ce3+ fractions and the lower band gap energies due to the electron transfer from DOPA to the CeO2 surface, DOPA still had a slightly negative effect on the HPO-like activity of CeO2 since they decreased the exposed Ce3+ sites. The DOPA-CeO2 nanocomposites with HPO-like activities could kill bacteria and trigger quorum-sensing signaling quenching, achieving a biofilm inhibition performance. Amazingly, 0.1% DOPA-CeO2 nanocomposite exhibited higher antibacterial activity and better biofilm suppression activities due to its HPO-like activity and positive zeta potential. The remarkable results demonstrated that DOPA, as a participant in the biofouling process, could enhance the antibacterial activity and antifouling performance of CeO2 nanoparticles at an appropriate concentration.

The role of [18 F]FDOPA PET as an adjunct to conventional MRI in the diagnosis of aggressive glial lesions.

BACKGROUND: Amino acid PET is recommended for the initial diagnosis of brain lesions, but its value for identifying aggressive lesions remains to be established. The current study therefore evaluates the added-value of dynamic [18 F]FDOPA PET as an adjunct to conventional MRI for determining the aggressiveness of presumed glial lesions at diagnosis. METHODS: Consecutive patients, with a minimal 1 year-follow-up, underwent contrast-enhanced MRI (CE MRI) and dynamic [18 F]FDOPA PET to characterize their suspected glial lesion. Lesions were classified semi-automatically by their CE MRI (MRI-/+), and PET parameters (static tumor-to-background ratio, TBR; dynamic time-to-peak ratio, TTPratio). Diagnostic accuracies of MRI and PET parameters for the differentiation of tumor aggressiveness were evaluated by chi-square test or receiver operating characteristic analyses. Aggressive lesions were either defined as lesions with dismal molecular characteristics based on the WHO 2021 classification of brain tumors or with compatible clinico-radiological profiles. Time-to-treatment failure (TTF) and overall survival (OS) were evaluated. RESULTS: Of the 109 patients included, 46 had aggressive lesions (45 confirmed by histo-molecular analyses). CE MRI identified aggressive lesions with an accuracy of 73%. TBRmax (threshold of 3.2), and TTPratio (threshold of 5.4 min) respectively identified aggressive lesions with an accuracy of 83% and 76% and were independent of CE MRI and clinical factors in the multivariate analysis. Among the MRI-lesions, 11/56 (20%) were aggressive and respectively 55% and 50% of these aggressive lesions showed high TBRmax and short TTPratio in PET. High TBRmax and short TTPratio in PET were significantly associated to poorer survivals (p ≤ 0.009). CONCLUSION: Dynamic [18 F]FDOPA PET provides a similar diagnostic accuracy as contrast enhancement in MRI to identify the aggressiveness of suspected glial lesions at diagnosis. Both methods, however, are complementary and [18 F]FDOPA PET may be a useful additional tool in equivocal cases.

Validation of cardiac image-derived input functions for functional PET quantification.

PURPOSE: Functional PET (fPET) is a novel technique for studying dynamic changes in brain metabolism and neurotransmitter signaling. Accurate quantification of fPET relies on measuring the arterial input function (AIF), traditionally achieved through invasive arterial blood sampling. While non-invasive image-derived input functions (IDIF) offer an alternative, they suffer from limited spatial resolution and field of view. To overcome these issues, we developed and validated a scan protocol for brain fPET utilizing cardiac IDIF, aiming to mitigate known IDIF limitations. METHODS: Twenty healthy individuals underwent fPET/MR scans using [18F]FDG or 6-[18F]FDOPA, utilizing bed motion shuttling to capture cardiac IDIF and brain task-induced changes. Arterial and venous blood sampling was used to validate IDIFs. Participants performed a monetary incentive delay task. IDIFs from various blood pools and composites estimated from a linear fit over all IDIF blood pools (3VOI) and further supplemented with venous blood samples (3VOIVB) were compared to the AIF. Quantitative task-specific images from both tracers were compared to assess the performance of each input function to the gold standard. RESULTS: For both radiotracer cohorts, moderate to high agreement (r: 0.60-0.89) between IDIFs and AIF for both radiotracer cohorts was observed, with further improvement (r: 0.87-0.93) for composite IDIFs (3VOI and 3VOIVB). Both methods showed equivalent quantitative values and high agreement (r: 0.975-0.998) with AIF-derived measurements. CONCLUSION: Our proposed protocol enables accurate non-invasive estimation of the input function with full quantification of task-specific changes, addressing the limitations of IDIF for brain imaging by sampling larger blood pools over the thorax. These advancements increase applicability to any PET scanner and clinical research setting by reducing experimental complexity and increasing patient comfort.

Study on the formation mechanism of blackening in damaged lotus rhizome epidermis: Effects of polyphenols and iron.

Lotus rhizome is an important aquatic vegetable, but the blackening of lotus rhizome epidermis (LRE) seriously affects its appearance and quality, which makes lotus rhizome products unmarketable. In this study, the effects of polyphenols and iron on the LRE color were studied to explore the possible mechanism of LRE blackening. Results indicated that the measurable total phenols contents in the mud treatment (MT) group were significantly reduced, and the total iron contents were significantly increased compared with the bruised treatment group (p < 0.05). The high-performance liquid chromatography results showed that the main polyphenols in LRE were dopa, gallocatechin, and catechin, as well as a small amount of catechol, epicatechin, proanthocyanidin B2, and proanthocyanidin C1. Moreover, the results of color difference and ultraviolet adsorption spectroscopy showed that there were obviously black or brown-gray of dopa (525 nm), gallocatechin (504.5 nm), and catechin (550 and 504.5 nm) with FeCl2. The simulated system treatment of LRE further confirmed that the chromaticity effect of dopa and iron in bruised LRE was similar to that of the MT group, whereas 1% (w/w) ascorbic acid, 2% (w/w) EDTA-2Na, or 3% (w/w) citric acid could solely prohibit the blackening. This suggested that the dopa in LRE and FeCl2 in mud may mainly combine into [2(DOPA-2H+)+Fe3+]- through non-covalent interaction, which leads to the blackening of bruised LRE under neutral conditions. These results can guide the storage of lotus rhizomes and improve the development of the lotus rhizome industry.

Alternative strategies for the recombinant synthesis, DOPA modification and analysis of mussel foot proteins - A case study for Mefp-3 from Mytilus edulis.

Mussel foot proteins (Mfps) possess unique binding properties to various surfaces due to the presence of L-3,4-dihydroxyphenylalanine (DOPA). Mytilus edulis foot protein-3 (Mefp-3) is one of several proteins in the byssal adhesive plaque. Its localization at the plaque-substrate interface approved that Mefp-3 plays a key role in adhesion. Therefore, the protein is suitable for the development of innovative bio-based binders. However, recombinant Mfp-3s are mainly purified from inclusion bodies under denaturing conditions. Here, we describe a robust and reproducible protocol for obtaining soluble and tag-free Mefp-3 using the SUMO-fusion technology. Additionally, a microbial tyrosinase from Verrucomicrobium spinosum was used for the in vitro hydroxylation of peptide-bound tyrosines in Mefp-3 for the first time. The highly hydroxylated Mefp-3, confirmed by MALDI-TOF-MS, exhibited excellent adhesive properties comparable to a commercial glue. These results demonstrate a concerted and simplified high yield production process for recombinant soluble and tag-free Mfp3-based proteins with on demand DOPA modification.

Feasibility of 18F-DOPA and 18F-FDG PET/CT for guiding decision-making for localized incidental neuroblastoma in infants under 18 months of age.

BACKGROUND: Neuroblastoma varies widely in risk. Risk indicators in infants with incidental neuroblastoma refine treatment confidence for observation or intervention. The potential of functional imaging, particularly PET/CT, remains to be defined. PROCEDURE: A retrospective review of infants under 18 months diagnosed with incidental neuroblastoma from 2008 to May 2022 in our institute was conducted. Before October 2015, incidental patients were treated similarly to symptomatic cases, undergoing biopsy or surgical excision upon diagnosis (early cohort). Post October 2015 (late cohort), treatment decisions were guided by PET/CT findings, with 18F-DOPA PET/CT confirming diagnosis and staging. For tumors with low 18F-FDG uptake, an expectant observation approach was considered. Patient characteristics, diagnostic methods, image findings at diagnosis, treatment courses, and responses were compared between cohorts. RESULTS: Thirty infants less than 18 months were identified with incidental neuroblastoma and completed PET/CT at diagnosis. The early and late cohorts each comprised 15 patients. In the late cohort, nine out of 15 patients (60%) presented with localized FDG non-avid tumors were offered the option of expectant observation. Of these, seven patients opted for observation, thereby avoiding surgery. Treatment outcomes were comparable between early and late cohorts, except for one mortality of a patient who, despite showing 18F-FDG activity, declined treatment. CONCLUSIONS: This study demonstrates the potential utility of 18F-DOPA and 18F-FDG PET/CT scans in aiding clinical decision-making for infants with localized, incidental neuroblastoma. Given the concerns regarding radiation exposure, such imaging may be valuable for cases with suspected metastasis, initial large tumor size, or growth during follow-up.

Quaternary Ammonium Assisted Synthesis of Melanin-like Poly(l-DOPA) Nanoparticles with a Boosted Photothermal Effect.

Poly(levodopa) nanoparticles (P(l-DOPA) NPs) are another kind of melanin mimetic besides well-established polydopamine nanoparticles (PDA NPs). Due to the presence of carboxyl groups, the oxidative polymerization of l-DOPA to obtain particles was not as efficient as that of dopamine. Several established methods toward P(l-DOPA) NP fabrication do not combine convenience, morphological regularity, size controllability, low cost, and adaptability to metal-free application scenarios. In this work, P(l-DOPA) NPs were successfully prepared in hot water with the assistant of organic quaternary ammonium, due to the extra physical cross-linking mediated by cations. The employed physical interactions could also be affected by quaternary ammonium structure (i.e., number of cation heads, length of alkyl chain) to achieve different polymerization acceleration effects. The obtained P(l-DOPA) NPs retained superior photothermal properties and outperformed PDA-based melanin materials. Furthermore, P(l-DOPA) NPs were used in photothermal tumor therapy and showed better efficacy. This study offers new insights into the synthesis of melanin-like materials, as well as new understanding of the interaction between quaternary ammonium and bioinspired polyphenolic materials.

Optimization of [18F]-FDOPA Brain PET Acquisition Times for Assessment of Parkinsonism in the Clinical Setting.

BACKGROUND AND PURPOSE: Fluorine 18-fluoro-L-dopa ([18F]-FDOPA) was approved by the FDA in 2019 and reimbursed by the Centers for Medicare & Medicaid Services in 2022 for use with PET to visualize dopaminergic nerve terminals in the striatum for evaluation of parkinsonism. We sought to determine the optimal image acquisition time for [18F]-FDOPA PET by evaluating rater-estimated FDOPA positivity and image quality across 4 time points. MATERIALS AND METHODS: Brain PET/CT was acquired 90 minutes following injection of 185 megabecquerel (5 mCi) of [18F]-FDOPA. PET was acquired in list mode for 20 minutes, and data were replayed to represent 15-, 10-, and 5-minute acquisitions. By means of MIMneuro, PET/MR imaging or PET/CT was independently graded for FDOPA positivity and image quality by 2 readers, blinded to the clinical report and diagnosis. Expert neuroradiologist clinical reads were used as the criterion standard. RESULTS: Twenty patients were included, average age 65.6 years, 55% women. Image-quality ratings decreased with shorter acquisition times for both readers (reader 1, ρ = 0.23, P = .044; reader 2, ρ = 0.24, P = .036), but there was no association between abnormality confidence scores and acquisition time (reader 1, ρ = -0.13, P = .250; reader 2, ρ = -0.19, P = .100). There was a high degree of consistency in intra- and interrater agreement and agreement with the expert reads when using acquisition times of ≥10 minutes (maximal confidence score consistency [ρ = 0.92] and interrater agreement [κ = 0.90] were observed at 15 minutes), while image quality was consistently rated as low and FDOPA positivity ratings were inconsistent when using a 5-minute acquisition time. CONCLUSIONS: Our study suggests that image-quality ratings were stable after 15 minutes and that between-subject abnormality detection rates were highly consistent between the 2 readers when acquired for at least 10 and up to 20 minutes but were inconsistent at 5 minutes. Shorter [18F]-FDOPA PET acquisition times may help maximize patient comfort while increasing throughput in the clinical setting.

Metabolization of Free Oxidized Aromatic Amino Acids by Saccharomyces cerevisiae.

The aromatic amino acids tryptophan, phenylalanine, and tyrosine are targets for oxidation during food processing. We investigated whether S. cerevisiae can use nonproteinogenic aromatic amino acids as substrates for degradation via the Ehrlich pathway. The metabolic fate of seven amino acids (p-, o-, m-tyrosine, 3,4-dihydroxyphenylalanine (DOPA), 3-nitrotyrosine, 3-chlorotyrosine, and dityrosine) in the presence of S. cerevisiae was assessed. All investigated amino acids except dityrosine were metabolized by yeast. The amino acids 3-nitrotyrosine and o-tyrosine were removed from the medium as fast as p-tyrosine, and m-tyrosine, 3-chlorotyrosine, and DOPA more slowly. In summary, 11 metabolites were identified by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS). DOPA, 3-nitrotyrosine, and p-tyrosine were metabolized predominantly to the Ehrlich alcohols, whereas o-tyrosine and m-tyrosine were metabolized predominantly to α-hydroxy acids. Our results indicate that nonproteinogenic aromatic amino acids can be taken up and transaminated by S. cerevisiae quite effectively but that decarboxylation and reduction to Ehrlich alcohols as the final metabolites is hampered by hydroxyl groups in the o- or m-positions of the phenyl ring. The data on amino acid metabolism were substantiated by the analysis of five commercial beer samples, which revealed the presence of hydroxytyrosol (ca. 0.01-0.1 mg/L) in beer for the first time.

Cerebrovascular Malformation Mimicking Recurrent Lymphoma on Dual Time-Point 18F-FDOPA PET.

ABSTRACT: Although 18F-FDG is the dominant radiotracer for PET imaging of hematological malignancies, radiolabeled amino acids have also been investigated to improve image quality in areas of high 18F-FDG uptake such as the central nervous system. We present a case of a 57-year-old woman who underwent an 18F-FDOPA scan for primary CNS lymphoma, which demonstrated an unexpected false-positive uptake in the right frontal lobe, due to a developmental venous anomaly.

Role of NT5DC2 in tyrosine hydroxylase phosphorylation based on the analysis of NT5DC2-binding proteins.

The gene encoding 5'-nucleotidase domain-containing protein 2 (NT5DC2) has been associated with neuropsychiatric disorders related to the abnormality of dopamine activity in the brain. However, its physiological functions remain unclear. In this study, we analyzed the features of NT5DC2 that influence its binding with tyrosine hydroxylase (TH) and its effects on dihydroxyphenylalanine (DOPA) synthesis, using NT5DC2 overexpressed in PC12D cells by the pCMV vector. Western blot analysis revealed that the purified NT5DC2-DYKDDDDK-tag (NT5DC2-tag) protein can bind with the phosphorylated form of recombinant human TH type 1 (rhTH1), apart from the endogenous TH in PC12D cells. Proteomic analysis by mass spectrometry revealed that the purified NT5DC2-tag protein has the potential to bind to 41 proteins with multiple phosphorylation sites in PC12D cells (NT5DC2 binding proteins: positive, 391 sites/41 proteins; and negative, 85 sites/27 proteins). Overexpression of NT5DC2 in PC12D cells decreased DOPA levels in the medium. When the lysate of PC12D cells overexpressing NT5DC2 was incubated at 37 °C, the phosphorylated form of endogenous TH in PC12D cells decreased. This decrease was also detected when phosphorylated rhTH1 was incubated with purified NT5DC2-tag. Overall, our results suggest that NT5DC2 regulates DOPA synthesis by promoting the dephosphorylation of TH, similar to a phosphatase. Therefore, our study provides useful information for understanding various disorders associated with abnormalities in dopamine levels in the brain.

Mechanisms underlying the efficacy and limitation of dopa and tetrahydrobiopterin therapies for the deficiency of GTP cyclohydrolase 1 revealed in a novel mouse model.

Dopa and tetrahydrobiopterin (BH4) supplementation are recommended therapies for the dopa-responsive dystonia caused by GTP cyclohydrolase 1 (GCH1, also known as GTPCH) deficits. However, the efficacy and mechanisms of these therapies have not been intensively studied yet. In this study, we tested the efficacy of dopa and BH4 therapies by using a novel GTPCH deficiency mouse model, Gch1KI/KI, which manifested infancy-onset motor deficits and growth retardation similar to the patients. First, dopa supplementation supported Gch1KI/KI mouse survival to adulthood, but residual motor deficits and dwarfism remained. Interestingly, RNAseq analysis indicated that while the genes participating in BH4 biosynthesis and regeneration were significantly increased in the liver, no significant changes were observed in the brain. Second, BH4 supplementation alone restored the growth of Gch1KI/KI pups only in early postnatal developmental stage. High doses of BH4 supplementation indeed restored the total brain BH4 levels, but brain dopamine deficiency remained. While total brain TH levels were relatively increased in the BH4 treated Gch1KI/KI mice, the TH in the striatum were still almost undetectable, suggesting differential BH4 requirements among brain regions. Last, the growth of Gch1KI/KI mice under combined therapy outperformed dopa or BH4 therapy alone. Notably, dopamine was abnormally high in more than half, but not all, of the treated Gch1KI/KI mice, suggesting the existence of variable synergetic effects of dopa and BH4 supplementation. Our results provide not only experimental evidence but also novel mechanistic insights into the efficacy and limitations of dopa and BH4 therapies for GTPCH deficiency.

Head-to-head comparison between [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT in a diverse cohort of patients with pheochromocytomas and paragangliomas.

PURPOSE: To compare the detection ability of 68Ga-labelled DOTA-l-Nal3-octreotide ([68Ga]Ga-DOTA-NOC) and 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine ([18F]DOPA) in patients with phaeochromocytomas and paragangliomas (PPGLs) of different origins and gene mutations, such as germline succinate dehydrogenase complex genes (SDHx). METHODS: Eighty-five patients with histopathologically confirmed PPGLs who underwent both [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT from March 2017 to June 2023 were enrolled in this retrospective study. For comparative analyses, PPGLs were classified as phaeochromocytoma (PCC), sympathetic paraganglioma (sPGL), and head/neck paraganglioma (HNPGL). Detection rates were analyzed on per-patient and per-lesion bases and compared using the Chi-square/Fischer's exact test. RESULTS: Among 85 patients with PPGLs (48 males; 43 years ± 17 [SD]), the patient-based detection rates of [68Ga]Ga-DOTA-NOC and [18F]DOPA PET/CT were 87.1% (74/85) and 89.4% (76/85), respectively (p = 0.634), and the lesion-based detection rates were 80.8% (479/593) and 71.2% (422/593), respectively (p < 0.001). Only one patient with a recurrent PCC presented double-negative imaging, while 66 patients exhibited double-positive imaging. The remaining patients were either [68Ga]Ga-DOTA-NOC-negative/[18F]DOPA-positive (n = 10) or [68Ga]Ga-DOTA-NOC-positive/[18F]DOPA-negative (n = 8). In subgroup analyses, [68Ga]Ga-DOTA-NOC PET/CT detected significantly more metastases of sPGL (91.1%, 236/259) and SDHx-related PPGL (89.6%, 86/96) than [18F]DOPA PET/CT (48.6%[126/259] and 50.0%[48/96], respectively; both p < 0.001). However, [18F]DOPA showed significantly higher detection rates of PCC in both primary/recurrent and metastatic lesions (94.3%[50/53] vs. 62.3%[33/53] and 87.9%[174/198] vs. 69.2%[137/198], respectively; both p < 0.001). Regarding metastases in different organs, [68Ga]Ga-DOTA-NOC PET/CT detected more lesions than [18F]DOPA PET/CT in bone (96.2%[176/183] vs. 66.1%[121/183]; p < 0.001) and lymph nodes (82.0%[73/89] vs. 53.9%[48/89]; p < 0.001) but less lesions in peritoneum (20%[4/20] vs. 100%[20/20]; p < 0.001). CONCLUSION: [68Ga]Ga-DOTA-NOC and [18F]DOPA are complementary in diagnosing PPGL under the appropriate clinical setting. [68Ga]Ga-DOTA-NOC should be considered as the ideal first-line tracer for detecting metastases of sPGL and SDHx-related tumours, whereas [18F]DOPA may be the optimal tracer for evaluating non-SDHx-related PCC, especially in detecting primary lesions and monitoring recurrence.

Análisis visual y semicuantitativo del 6-[18F]FDOPA PET/TC en pacientes con tumores cerebrales ante la sospecha de recurrencia tumoral versus radionecrosis / VAnálisis visual y semicuantitativo del 6-[18F]FDOPA PET/TC en pacientes con tumores cerebrales ante la sospecha de recurrencia tumoral versus radionecrosis

Introducción La tomografía por emisión de positrones (PET) con aminoácidos es una herramienta recomendada por las principales sociedades de neuroimagen, en el diagnóstico diferencial entre radionecrosis (RNC) y recurrencia tumoral (RT) en los tumores cerebrales, sin embargo, su uso en nuestro pais aún es limitado. El objetivo de este trabajo es presentar nuestra experiencia con 6-[18F]FDOPA PET/TC (FDOPA) en tumores cerebrales (primarios y M1), comparando estos resultados con otros publicados. Material y métodos Estudio retrospectivo de 62 pacientes con sospecha de RT: 42 metástasis cerebrales (M1) y 20 primarios, a los que se les realizó una FDOPA. Las imágenes fueron analizadas visual y semicuantitativamente, obteniendo el SUVmax y los ratios SUVmaxlesión/SUVmaxestriado (L/E) y SUVmaxlesión/SUVmaxcortex (L/C). Se analizó la validez diagnóstica de la PET y se calcularon los puntos de corte con mayor rendimiento. Los resultados de la PET se compararon con la evolución clínico-radiológica y/o con la histopatología. Resultados Se identificó RT en el 49% de las M1 y en el 76% de los primarios cerebrales. La interpretación de la FDOPA con mejores resultados fue la conjunta; visual y semicuantitativa, con una sensibilidad y especificidad en los primarios del 94 y 80% y en las M1 del 96 y 72%, respectivamente. Los puntos de corte con mejor rendimiento diagnóstico fueron L/C 1,44 en M1 y L/C 1,55 en primarios. Existen resultados discrepantes con otros publicados. Conclusión La FDOPA PET/TC es una herramienta útil en el diagnóstico diferencial entre RT y RNC en tumores cerebrales. Es necesario una estandarización que contribuya a homogeneizar los resultados de la FDOPA a nivel intercentro (AU)

Introduction Amino acid PET is a tool recommended by the main neuroimaging societies in the differential diagnosis between radionecrosis (RNC) and tumour recurrence (TR) in brain tumours, but its use in our country is still limited. The aim of this work is to present our experience with 6-[18F]FDOPA PET/CT (FDOPA) in brain tumours (primary and M1), comparing these results with other published results. Material and methods Retrospective study of 62 patients with suspected tumour recurrence (TR): 42 brain metastases (M1) and 20 primary, who underwent FDOPA. Images were analysed visually and semi-quantitatively, obtaining SUVmax and SUVmaxlesion/SUVmaxstriatum (L/S) and SUVmaxlesion/SUVmaxcortex (L/C) ratios. The diagnostic validity of PET was analysed and the best performing cut-off points were calculated. PET results were compared with clinical-radiological follow-up and/or histopathology. Results TR was identified in 49% of M1 and 76% of brain primaries. The best performing FDOPA interpretation was visual and semi-quantitative, with a sensitivity and specificity in primaries of 94% and 80% and in M1s of 96% and 72% respectively. The cut-off points with the best diagnostic performance were L/C1.44 in M1 and L/C1.55 in primaries. There are discrepant results with other published results. Conclusion FDOPA PET/CT is a useful tool in the differential diagnosis between recurrence and RNC in brain tumours. It is needed a standardization to contribute to homogenise FDOPA results a inter-centre level (AU)

Enhanced the intrinsic oxidase-like activity of chiral carbon dots via manganese doping for selective catalytic oxidation.

It is highly desirable to design and construct chemical catalysts with high activity and specificity as the alternatives of natural enzymes for industrial application. Chiral carbon dots (CDs), possessing both the intrinsic enzyme-like activity and specific recognition ability, are one of good candidates for enzyme-like catalysts. However, their catalytic activity is far from that of natural enzymes and needs to be enhanced. In this work, the modulation of the chiral structure and catalytic activity of chiral CDs with intrinsic oxidase-like activity was implemented by manganese (Mn) doping. Under the light condition, chiral CDs (l-Ser-CDs and d-Ser-CDs) derived from chiral serine (Ser) show weak catalytic activity and low selectivity toward the oxidation of L type of dopamine (l-DOPA), whereas the Mn functionalized chiral CDs (l-Mn-CDs or d-Mn-CDs) exhibit 6.9 times higher in catalytic activity and 2.9 times in selectivity ratio (SR) than Ser-CDs. Mn-CDs involve two-path catalytic process, in which the photogenerated electrons could reduce O2 to O2- as the active species and the holes would oxidize DOPA directly. Moreover, doping of Mn enables the CDs to generate more O2-. Besides, l-Mn-CDs have higher catalytic activity than that of d-Mn-CDs (+54.2 %), and the chiral Mn-CDs have stronger selective adsorption capacity towards chiral DOPA than Ser-CDs. Our work provides a new method for designing and preparing novel chiral artificial enzymes.

Hyaluronic acid-functionalized graphene-based nanohybrids for targeted breast cancer chemo-photothermal therapy.

Nanomaterials' application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines' translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials' surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics' action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells' viability to just 23 %, showcasing their potential chemo-photothermal therapy.

Self-Assembled Materials Based on Fully Aromatic Peptides: The Impact of Tryptophan, Tyrosine, and Dopa Residues.

Peptides are able to self-organize in structural elements including cross-ß structures. Taking advantage of this tendency, in the last decades, peptides have been scrutinized as molecular elements for the development of multivalent supramolecular architectures. In this context, different classes of peptides, also with completely aromatic sequences, were proposed. Our previous studies highlighted that the (FY)3 peptide, which alternates hydrophobic phenylalanine and more hydrophilic tyrosine residues, is able to self-assemble, thanks to the formation of both polar and apolar interfaces. It was observed that the replacement of Phe and Tyr residues with other noncoded aromatic amino acids like 2-naphthylalanine (Nal) and Dopa affects the interactions among peptides with consequences on the supramolecular organization. Herein, we have investigated the self-assembling behavior of two novel (FY)3 analogues with Trp and Dopa residues in place of the Phe and Tyr ones, respectively. Additionally, PEGylation of the N-terminus was analyzed too. The supramolecular organization, morphology, and capability to gel were evaluated using complementary techniques, including fluorescence, Fourier transform infrared spectroscopy, and scanning electron microscopy. Structural periodicities along and perpendicular to the fiber axis were detected by grazing incidence wide-angle X-ray scattering. Finally, molecular dynamics studies provided interesting insights into the atomic structure of the cross-ß that constitutes the basic motif of the assemblies formed by these novel peptide systems.