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1.
Clin Nucl Med ; 49(3): 232-233, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38306374

RESUMO

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.


Assuntos
Di-Hidroxifenilalanina/análogos & derivados , Fluordesoxiglucose F18 , Linfoma , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Linfoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos
2.
J Fluoresc ; 34(2): 765-774, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37358758

RESUMO

Sensitive and convenient strategy of tyrosinase (TYR) and its inhibitor atrazine is in pressing demand for essential research as well as pragmatic application. In this work, an exquisite label-free fluorometric assay with high sensitivity, convenience and efficiency was described for detecting TYR and the herbicide atrazine on the basis of fluorescent nitrogen-doped carbon dots (CDs). The CDs were prepared via one-pot hydrothermal reaction starting from citric acid and diethylenetriamine. TYR catalyzed the oxidation of dopamine to dopaquinone derivative which could quench the fluorescence of CDs through a fluorescence resonance energy transfer (FRET) process. Thus, a sensitive and selective quantitative evaluation of TYR can be constructed on the basis of the relationship between the fluorescence of CDs and TYR activity. Atrazine, a typical inhibitor of TYR, inhibited the catalytic activity of TYR, leading to the reduced dopaquinone and the fluorescence was retained. The strategy covered a broad linear range of 0.1-150 U/mL and 4.0-80.0 nM for TYR and atrazine respectively with a low detection limit of 0.02 U/mL and 2.4 nM/mL. It is also demonstrated that the assay can be applied to detect TYR and atrazine in spiked complex real samples, which provides infinite potential in application of disease monitoring along with environmental analysis.


Assuntos
Atrazina , Di-Hidroxifenilalanina/análogos & derivados , Pontos Quânticos , Monofenol Mono-Oxigenase/análise , Carbono , Atrazina/análise , Benzoquinonas , Corantes Fluorescentes , Nitrogênio
3.
Gastrointest Endosc ; 99(2): 227-236, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37838323

RESUMO

BACKGROUND AND AIMS: Small-bowel neuroendocrine tumors (NETs) are slow growing, clinically silent tumors whose prognosis depends on disease stage. Members of kindreds with a familial form of small intestinal NETs (SI-NETs) represent a high-risk population for whom early detection improves disease outcome. Our aim was to determine the utility of small-bowel capsule endoscopy (SB-CE) for screening high-risk asymptomatic relatives from kindreds with familial carcinoid. METHODS: One hundred seventy-four asymptomatic subjects with a family history (≥2 family members) of SI-NETs were screened under Protocol NCT00646022, Natural History of Familial Carcinoid Tumor at the National Institutes of Health. All patients were imaged with SB-CE and 18fluoro-dihydroxphenylalanine (18F-DOPA) positron emission tomography (PET)/CT, and results were independently analyzed. Patients with a positive imaging study underwent surgical exploration. RESULTS: Thirty-five of 174 asymptomatic subjects screened for SI-NETs were positive on either SB-CE or 18F-DOPA PET. Thirty-two of 35 patients with a positive study were confirmed at surgery. SB-CE was positive in 28 of 32 patients with confirmed tumors for a per-patient sensitivity of 87.5%. SB-CE had a specificity of 97.3% and a negative predictive value of 96.5%. The average tumor number and size were 7.7 and 5.0 mm, respectively, and 81.2% of patients had multiple tumors. 18F-DOPA PET/CT had a similar sensitivity of 84% versus surgery. CONCLUSIONS: SB-CE is a sensitive and specific method comparable with 18F-DOPA PET/CT for screening high-risk patients with familial SI-NET. (Clinical trial registration number: NCT00646022.).


Assuntos
Endoscopia por Cápsula , Tumor Carcinoide , Di-Hidroxifenilalanina/análogos & derivados , Tumores Neuroendócrinos , Humanos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Prospectivos , Tumor Carcinoide/diagnóstico por imagem
4.
Anal Biochem ; 655: 114856, 2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-35964734

RESUMO

Tyrosinase catalyzes the oxidation of l-tyrosine in two stages to produce l-dopa and l-dopaquinone stepwise, and l-dopaquinone is subsequently converted to dopachrome. Most of the conventional analyses subjected only one-step reaction from l-tyrosine to l-dopa or from l-dopa to l-dopaquinone. In this study, kinetic analyses of two-steps oxidation of l-tyrosine with tyrosinase were made by capillary electrophoresis/dynamic frontal analysis (CE/DFA). When l-dopa was introduced into a capillary as a sample plug in a CE/DFA format, the enzymatic oxidation continuously occurred during the electrophoresis, and the product l-dopaquinone was subsequently converted to dopachrome which was detected as a plateau signal. A Michaelis-Menten constant of the second-step kinetic reaction, Km,Do, was determined as 0.45 ± 0.03 mmol L-1. In the analysis of the first-step kinetic reaction from l-tyrosine to l-dopa, l-dopa was not resolved by CE/DFA because both l-tyrosine and l-dopa are electrically neutral. The l-dopa formed and co-migrated at the l-tyrosine zone was calibrated beforehand with the final product of dopachrome detected as a plateau signal. Constantly formed l-dopa was successfully detected as a plateau signal of dopachrome, and a Michaelis-Menten constant of Km,Ty was also determined as 0.061 ± 0.009 mmol L-1 by the CE/DFA. CE/DFA is applicable to two-steps enzymatic reactions.


Assuntos
Monofenol Mono-Oxigenase , Tirosina , Benzoquinonas , Di-Hidroxifenilalanina/análogos & derivados , Eletroforese Capilar , Cinética , Monofenol Mono-Oxigenase/metabolismo
5.
Pediatr Blood Cancer ; 69(11): e29910, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35920594

RESUMO

PURPOSE: To evaluate the prognostic value of texture analysis of the primary tumour with 18 fluorine-dihydroxyphenylalanine positron emission tomography/X-ray computed tomography (18 F-DOPA PET/CT) in patients affected by high-risk neuroblastoma (HR-NBL). METHODS: We retrospectively analysed 18 patients with HR-NBL, which had been prospectively enrolled in the course of a previous trial investigating the diagnostic role of 18 F-DOPA PET/CT at the time of the first onset. Texture analysis of the primary tumour was carried out on the PET images using LifeX. Conventional indices, histogram parameters, grey level co-occurrence (GLCM), run-length (GLRLM), neighbouring difference (NGLDM) and zone-length (GLZLM) matrices parameter were extracted; their values were compared with the overall metastatic load, expressed by means of whole-body metabolic burden (WBMB) score and the progression-free/overall survival (PFS and OS). RESULTS: There was a direct correlation between WBMB and radiomics parameter describing uptake intensity (SUVmean : p = .004) and voxel heterogeneity (entropy: p = .026; GLCM_Contrast: p = .001). Conversely, texture indices of homogeneity showed an inverse correlation with WBMB (energy: p = .026; GLCM_Homogeneity: p = .006). On the multivariate model, WBMB (p < .01) and the first standardised uptake value (SUV) quartile (p < .001) predicted PFS; OS was predicted by WBMB and the N-myc proto-oncogene protein (MYCN) amplification (p < .05) for both. CONCLUSIONS: Textural parameters describing heterogeneity and metabolic intensity of the primary HR-NBL are closely associated with its overall metastatic burden. In turn, the whole-body tumour load appears to be one of the most relevant predictors of progression-free and overall survival.


Assuntos
Neuroblastoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Di-Hidroxifenilalanina/análogos & derivados , Flúor , Fluordesoxiglucose F18 , Humanos , Proteína Proto-Oncogênica N-Myc , Neuroblastoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Estudos Retrospectivos
6.
Clin Nucl Med ; 47(11): 931-935, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-35961651

RESUMO

OBJECTIVE: The aim of this study was to compare 2 imaging tracers, 18 F-DOPA and 18 F-DTBZ, for PET/CT imaging in idiopathic Parkinson disease (PD). METHODS: We recruited 32 PD patients and 12 healthy controls in this study. All subjects underwent both 18 F-DOPA and 18 F-DTBZ PET/CT, and the results were interpreted by visual analysis and semiquantitative analysis (specific uptake ratios [SURs]). A 1-way analysis of variance was used to compare the clinical data and the SURs among the patients at different stages. Regression analysis was performed to analyze the correlation between the SURs and the clinical data. RESULTS: Among the PD patients, there were 7 patients in Hoehn and Yahr stage I, 14 patients in stage II, and 11 patients in stage III. Linear correlation was found in striatal SURs between the 2 tracers ( P < 0.05). In patients of early stages, the striatal SUR decrease percent of 2 tracers had no statistical difference (paired t test, P > 0.05). By initial visual analysis, all the patients were interpreted as positive with 18 F-DBTZ (6 unilaterally, 26 bilaterally), and 31 cases were regarded as positive with 18 F-DOPA (8 unilaterally, 23 bilaterally). After setting the upper limit of SUR images with the putamen SURs of healthy controls (SUR T ), all patients were interpreted as positive with both tracers ( 18 F-DTBZ: 5 unilaterally, 27 bilaterally; 18 F-DOPA: 4 unilaterally, 28 bilaterally). CONCLUSION: 18 F-DTBZ and 18 F-DOPA could reflect the same level of dopaminergic neuron degeneration for PD in early stages, and they have the consistent visual analysis results.


Assuntos
Doença de Parkinson , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Doença de Parkinson/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos
7.
Hell J Nucl Med ; 25(2): 213-215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913869

RESUMO

Unruptured brain arteriovenous malformations (AVM) have a heterogeneous clinical presentation, mainly related to the presence of intracerebral hemorrhage. We report the diagnosis of AVM in a patient with Parkinson's disease (PD), who undergone positron emission tomography/magnetic resonance imaging (PET/MRI) molecular brain imaging with fluorine-18-dihydroxyphenylalanine (18F-DOPA). This case suggests that AVM may be occasionally recognized in molecular imaging studies using positron-emitting amino acids. Magnetic resonance imaging with susceptibility-weighted imaging (SWI) sequences and 3D time of flight (TOF) reconstruction may contribute to manage patients with AVM.


Assuntos
Malformações Arteriovenosas , Tomografia Computadorizada por Raios X , Encéfalo , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons
8.
Clin Nucl Med ; 47(8): 717-718, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35797630

RESUMO

ABSTRACT: Orbital foci of increased uptake are sometimes visualized on 18F-FDOPA PET/CT, but the literature remains poor as to their nature. The orbit is indeed a rare site of metastatic involvement. Given this low probability of metastatic location, the question of an incidental benign finding may arise. We reviewed all 18F-FDOPA PET/CT examinations performed at our institution between January 2015 and May 2021: 4/149 patients presented at least 1 orbital focus of increased uptake, all of them presented a metastatic small intestine neuroendocrine tumor. Somatostatin receptor expression was confirmed using 68Ga-DOTATOC PET/CT supporting the hypothesis of genuine metastases.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Neoplasias Intestinais/diagnóstico por imagem , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
9.
Mov Disord ; 37(10): 2057-2065, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35765711

RESUMO

BACKGROUND: Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood-brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD. OBJECTIVE: Here, we report a prospective, single-arm, nonrandomized, proof-of-concept, phase I clinical trial (NCT03608553 amended) in PD with dementia to test the safety and feasibility of striatal BBB opening in PD patients. METHODS: Seven PD patients with cognitive impairment were treated for BBB opening in the posterior putamen. This was performed in two sessions separated by 2 to 4 weeks, where the second session included bilateral putamina opening in 3 patients. Primary outcome measures included safety and feasibility of focal striatal BBB opening. Changes in motor and cognitive functions, magnetic resonance imaging (MRI), 18 F-fluorodopa (FDOPA), and ß-amyloid PET (positron emission tomography) images were determined. RESULTS: The procedure was feasible and well tolerated, with no serious adverse events. No neurologically relevant change in motor and cognitive (battery of neuropsychological tests) functions was recognized at follow-up. MRI revealed putamen BBB closing shortly after treatment (24 hours to 14 days) and ruled out hemorrhagic and ischemic lesions. There was a discrete but significant reduction in ß-amyloid uptake in the targeted region and no change in FDOPA PET. CONCLUSIONS: These initial results indicate that FUS-mediated striatal BBB opening is feasible and safe and therefore could become an effective tool to facilitate the delivery of putative neurorestorative molecules in PD. © 2022 International Parkinson and Movement Disorder Society.


Assuntos
Doença de Alzheimer , Demência , Doença de Parkinson , Peptídeos beta-Amiloides , Barreira Hematoencefálica , Corpo Estriado/diagnóstico por imagem , Corpo Estriado/patologia , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Estudos Prospectivos
10.
J Neurooncol ; 158(3): 323-330, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35583721

RESUMO

PURPOSE: In-field high-grade glioma (HGG) recurrence is a common challenge with limited treatment options, including re-irradiation. The radiotracer 3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine (18F-DOPA) crosses the blood brain barrier and demonstrates high uptake in tumor, but low uptake in normal tissue. This study investigated whether 18F-DOPA positron emission tomography (PET) and MRI guided re-irradiation for recurrent HGG may improve progression free survival (PFS). METHODS: Adults with recurrent or progressive HGG previously treated with radiation were eligible. The primary endpoint was a 20% improvement from the historical control PFS at 3 months (PFS3) of 20% with systemic therapy alone. Re-RT dose was 35 Gy in 10 fractions. The target volume was MRI T1 contrast-enhancement defined tumor plus 18F-DOPA PET defined tumor. RESULTS: Twenty patients completed treatment per protocol. Diagnosis was most commonly glioblastoma, IDH-wildtype (60%). MRI-defined volumes were expanded by a median 43% (0-436%) by utilizing 18F-DOPA PET. PFS3 was 85% (95% CI 63.2-95.8%), meeting the primary endpoint of PFS3 ≥ 40%. With 9.7 months median follow-up, 17 (85%) had progressed and 15 (75%) had died. Median OS from re-RT was 8.8 months. Failure following re-RT was within both the MRI and PET tumor volumes in 75%, MRI only in 13%, PET only in 0%, and neither in 13%. Four (20%) patients experienced grade 3 toxicity, including CNS necrosis (n = 2, both asymptomatic with bevacizumab initiation for radiographic findings), seizures (n = 1), fatigue (n = 1), and nausea (n = 1). No grade 4-5 toxicities were observed. CONCLUSION: 18F-DOPA PET-guided re-irradiation for progressive high-grade glioma appears safe and promising for further investigation.


Assuntos
Neoplasias Encefálicas , Glioma , Reirradiação , Adulto , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Di-Hidroxifenilalanina/análogos & derivados , Glioma/diagnóstico por imagem , Glioma/tratamento farmacológico , Glioma/radioterapia , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/radioterapia , Tomografia por Emissão de Pósitrons/métodos , Reirradiação/métodos
11.
Endocrine ; 77(1): 143-150, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35489000

RESUMO

PURPOSE: 18F-DOPA Positron Emission Tomography/Computed Tomography (18F-DOPA PET/CT) is a sensitive functional imaging method (65-75%) for detecting disease localization in medullary thyroid cancer (MTC). We aimed: (i) to assess the clinical usefulness of 18F-DOPA PET/CT in patients with MTC and elevated calcitonin (Ctn) and CEA levels and, (ii) to evaluate changes in disease management secondary to the findings encountered with this methodology. METHODS: Thirty-six patients with MTC and Ctn levels ≥150 pg/ml were prospectively included. Neck ultrasound, chest contrast-enhanced CT, liver magnetic resonance imaging/abdominal three-phase contrast-enhanced CT and bone scintigraphy were carried out up to 6 months before the 18F DOPA PET/CT. RESULTS: Seventy eight percent of patients were female and 27% had hereditary MTC. Median Ctn level was 1450 pg/ml [150-56620], median CEA level 413 ng/ml [2.9-7436]. Median Ctn DT was 37.5 months [5.7-240]; median CEA DT was 31.8 [4.9-180]. 18F-DOPA PET/CT was positive in 33 patients (91.6%); in 18 (56%) uptake was observed in lymph nodes in the neck or mediastinum, in seven cases (22%) distant metastases were diagnosed, and in eight additional patients (24%) both locoregional and distant sites of disease were found. Ctn and CEA levels were higher in patients with ≥3 foci of distant metastases. In 14 patients (38.8%), findings on 18F-DOPA PET/CT led to changes in management; surgery for locoregional lymph nodes was the most frequent procedure in 8 patients (22%). CONCLUSION: 18F-DOPA PET/CT was useful for the detection of recurrent disease in MTC, providing incremental value over conventional imaging procedures that led to modification in treatment strategies in nearly 40% of patients.


Assuntos
Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Calcitonina , Antígeno Carcinoembrionário , Carcinoma Neuroendócrino/patologia , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Neoplasias da Glândula Tireoide/patologia
12.
Int J Mol Sci ; 23(5)2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35269556

RESUMO

Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)-positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18F-DOPA-PET uptake and LAT1 expression, and we explored the role of miR-375 and putative target genes. A consecutive series of 58 Pheo patients were retrospectively analyzed, performing 18F-DOPA-PET in 32/58 patients. Real-time quantitative PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wingless/Integrated pathways. Principal germline mutations associated with hereditary Pheo were also studied. Pheo tissues had significantly higher LAT1, LAT2, and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. Yes-associated protein 1 and tankyrase 1 were upregulated, while beta-catenin, axin2, monocarboxylate transporter 8, and Frizzled 8 were downregulated. A positive relationship was found between 18F-DOPA-PET SUV mean and LAT1 gene expression and for 24 h-urinary norepinephrine and LAT1. This is the first experimental evidence of 18F-DOPA uptake correlating with LAT1 overexpression. We also demonstrated miR-375 overexpression and downregulated (Wnt) signaling and identified the Hippo pathway as a new potentially oncogenic feature of Pheo.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Transportador 1 de Aminoácidos Neutros Grandes/genética , MicroRNAs/genética , Feocromocitoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Neoplasias das Glândulas Suprarrenais/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Di-Hidroxifenilalanina/administração & dosagem , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/urina , Feniletanolamina N-Metiltransferase/genética , Feocromocitoma/genética , Feocromocitoma/patologia , Feocromocitoma/urina , Estudos Retrospectivos , Carga Tumoral , Regulação para Cima , Via de Sinalização Wnt
13.
Q J Nucl Med Mol Imaging ; 66(2): 141-147, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35343670

RESUMO

6-[18F]-L-fluoro-L-3, 4-dihydroxyphenylalanine (18F-DOPA) PET/CT can be a useful tool for the detection of different neuroendocrine tumors (NETs). The main determinants of 18F-DOPA uptake and retention by NETs are related to expression of LAT1/LAT2 transporters, expression and activity of AADC and biochemical phenotype, all being intimately inter-connected to their embryological origin. In order to improve sensitivity of 18F-DOPA PET, it is of main importance to perform indivisualized imaging protocols across primaries. This review provides a practical approach for performing well-tailored imaging protocols and describes the clinical value of the recommended radiopharmaceuticals.


Assuntos
Neoplasias das Glândulas Suprarrenais , Tumores Neuroendócrinos , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Imagem Molecular , Tumores Neuroendócrinos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Literatura de Revisão como Assunto
14.
Med Mycol ; 60(2)2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35064672

RESUMO

Eumycetoma is a neglected tropical disease, and Madurella mycetomatis, the most common causative agent of this disease forms black grains in hosts. Melanin was discovered to be one of the constituents in grains. Melanins are hydrophobic, macromolecular pigments formed by oxidative polymerisation of phenolic or indolic compounds. M. mycetomatis was previously known to produce DHN-melanin and pyomelanin in vitro. These melanin was also discovered to decrease M. mycetomatis's susceptibility to antifungals itraconazole and ketoconazole in vitro. These findings, however, have not been confirmed in vivo. To discover the melanin biosynthesis pathways used by M. mycetomatis in vivo and to determine if inhibiting melanin production would increase M. mycetomatis's susceptibility to itraconazole, inhibitors targeting DHN-, DOPA- and pyomelanin were used. Treatment with DHN-melanin inhibitors tricyclazole, carpropamid, fenoxanil and DOPA-melanin inhibitor glyphosate in M. mycetomatis infected Galleria mellonella larvae resulted in presence of non-melanized grains. Our finding suggested that M. mycetomatis is able to produce DOPA-melanin in vivo. Inhibiting DHN-melanin with carpropamid in combination with the antifungal itraconazole also significantly increased larvae survival. Our results suggested that combination treatment of antifungals and melanin inhibitors can be an alternative treatment strategy that can be further explored. Since the common black-grain eumycetoma causing agents uses similar melanin biosynthesis pathways, this strategy may be applied to them and other eumycetoma causative agents. LAY SUMMARY: Melanin protects fungi from environmental stress and antifungals. We have discovered that Madurella mycetomatis produces DHN-, pyomelanin and DOPA-melanin in vivo. Inhibiting M. mycetomatis DHN-melanin biosynthesis increases therapeutic value of the antifungal itraconazole in vivo.


Assuntos
Madurella , Micetoma , Animais , Antifúngicos/farmacologia , Di-Hidroxifenilalanina/análogos & derivados , Itraconazol/farmacologia , Micetoma/tratamento farmacológico , Micetoma/veterinária
15.
Clin Nucl Med ; 47(4): 294-298, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35067541

RESUMO

PURPOSE: Peritoneal carcinomatosis (PC) concerns up to 30% of patients with a neuroendocrine tumor (NET), especially of the small intestine. Aggressive management of carcinomatosis seems to be justified, especially with regard to possible mechanical complications. 18F-FDOPA PET/CT is known to be the most sensitive imaging modality for the detection of small bowel NET metastases, yet its performance in the detection of PC is not well studied. The main objective of our study is to evaluate the performances of preoperative 18F-FDOPA PET/CT in the prediction of surgical peritoneal cancer index. METHODS: All patients referred to our center for an 18F-FDOPA PET/CT from October 2017 to January 2021 were retrospectively screened. Images were analyzed by a blinded nuclear medicine physician, and peritoneal abnormalities were reported to comply with the surgical peritoneal cancer index standard. Per patient analysis and per region analysis were then conducted. RESULTS: Thirty-three patients were included; 6 patients (35 regions) presented a peritoneal carcinosis. Peritoneal Carcinomatosis Index (PCI) estimated on 18F-FDOPA PET/CT was significantly and strongly correlated to surgical PCI (r = 0.96, P < 0.001). Patient-based sensitivity, specificity, negative predictive value, and positive predictive value for 18F-FDOPA PET/CT were 100%, 93%, 100%, and 75%, respectively. The agreement between 18F-FDOPA and surgery regarding PC was excellent (Cohen κ = 0.82 on per patient analysis, 0.74 on per region analysis). CONCLUSIONS: A preoperative estimation of PCI is achievable based on 18F-FDOPA PET/CT for small intestine NET and could allow to optimize surgical procedures and patient selection.


Assuntos
Tumores Neuroendócrinos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Di-Hidroxifenilalanina/análogos & derivados , Humanos , Intestino Delgado/diagnóstico por imagem , Intestino Delgado/patologia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos
16.
Food Chem ; 370: 131295, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34788955

RESUMO

Browning seriously causes postharvest deterioration of the yellow cultivars of Flammulina filiformis, yet the browning process and its mechanism have not been described. Changes of L*, a*, b* values, the browning and whiteness index during air contacted storage were evaluated, uncovering the great loss of brightness and meanwhile the accumulation of yellowness and redness. Browning tissue showed an increase of malondialdehyde, total phenolics, and browning-related enzyme activities of polyphenol oxidase and peroxidase, in contrast to the decrease of bioprotective catalase, superoxide, and dismutase. Non-targeted metabolomics revealed an upregulation of melanin synthesis under oxidation stress, and targeted LC-MS/MS verified the upregulation of l-dopa (3,4-dihydroxy-l-phenylalanine) during browning. Pyrrole-2,3,5-tricarboxylic acid was identified in the degradation products of browning pigments after alkaline hydrogen peroxide by LC-MS/MS, suggesting the existence of 5,6-dihydroxyindole-2-carboxylic acid derived units of eumelanin. Therefore, the biosynthesis of eumelanin via l-dopa pathway could participate in the enzymatic browning of postharvest F. filiformis.


Assuntos
Agaricales , Flammulina , Cromatografia Líquida , Di-Hidroxifenilalanina/análogos & derivados , Metabolômica , Espectrometria de Massas em Tandem
17.
Mov Disord ; 37(3): 629-634, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34762337

RESUMO

BACKGROUND: Mutations in GBA1 are a common genetic risk factor for parkinsonism; however, penetrance is incomplete, and biomarkers of future progression to parkinsonism are needed. Both nigral sonography and striatal [18 F]-FDOPA PET assay dopamine system health, but their utility and coherence in this context are unclear. OBJECTIVE: The aim of this study is to evaluate the utility and coherence of these modalities in GBA1-associated parkinsonism. METHODS: A total of 34 patients with GBA1 mutations (7 with parkinsonism) underwent both transcranial studies for substantia nigra echogenicity and [18 F]-FDOPA PET to determine striatal tracer-specific uptake (Ki ). RESULTS: Larger nigral echogenic areas and reduced striatal Ki were exclusively observed in parkinsonian patients. Sonographic and PET measurements showed strong inverse correlations but only in individuals with clinical parkinsonism. CONCLUSIONS: Close correspondence between nigral echogenicity and striatal presynaptic dopamine synthesis capacity observed only in GBA1 carriers with parkinsonism provides validation that these two modalities may conjointly capture aspects of the biology underlying clinical parkinsonism but raises questions about their utility as predictive tools in at-risk subjects. © 2022 International Parkinson and Movement Disorder Society.


Assuntos
Glucosilceramidase/genética , Transtornos Parkinsonianos , Di-Hidroxifenilalanina/análogos & derivados , Dopamina , Humanos , Mutação/genética , Transtornos Parkinsonianos/genética , Tomografia por Emissão de Pósitrons/métodos , Ultrassonografia
18.
Clin Nucl Med ; 47(3): 251-252, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34507330

RESUMO

ABSTRACT: We report the case of a 75-year-old woman with liver metastasis as a recurrence of a pheochromocytoma resected 10 years ago, with a rare germline mutation in transmembrane protein 127, falsely negative on 18F-FDOPA and 18F-FDG PET/CT scans but strongly positive on 123I-MIBG scintigraphy and on 68Ga-DOTATOC PET/CT. Functional imaging has a key role in diagnosis of pheochromocytoma and paraganglioma, especially 18F-FDOPA shows very high sensitivity and specificity. However, 18F-FDOPA might be falsely negative in some of these tumors, depending on specific mutations, and thus MIBG or 68Ga-DOTATOC imaging could be an alternative.


Assuntos
Neoplasias das Glândulas Suprarrenais , Feocromocitoma , 3-Iodobenzilguanidina , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/genética , Idoso , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Fluordesoxiglucose F18 , Humanos , Radioisótopos do Iodo , Mutação , Octreotida/análogos & derivados , Compostos Organometálicos , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/genética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
19.
J Nucl Cardiol ; 29(3): 1280-1290, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33426586

RESUMO

BACKGROUND: Dysfunction and denervation of myocardial nor-adrenergic sympathetic neurons has been documented in IPD patients with dysautonomia. The aim of this study was to evaluate the feasibility of single tracer imaging of myocardial sympathetic and cerebral striatal involvement in these patients. METHODS: Twenty-two controls (mean-age 59.09 ± 12.39 years, 15 men) with no clinical autonomic-dysfunction and normal striatal-uptake in 18F-FDOPA-PET/CT; and 28 patients (mean-age 58.18 ± 8.25 years, 18 men) with autonomic-dysfunction (in Autonomic Function Tests) and striatal dopaminergic-dysfunction were enrolled. Both cardiac-PET/CT (40 minutes post IV-injection of 185-259MBq 18F-FDOPA) and Brain-PET/CT (60 minutes post-IV) were acquired in same session. ROIs were drawn over the entire left ventricular myocardium, individual walls and mediastinum for quantification. Patients and controls were followed-up for 26.93 ± 5.43 months and 37.91 ± 8.63 months, respectively. RESULTS: Striatal and myocardial-parameters were significantly lower in patients compared to controls; with Myocardium/mediastinal ratio (MwMR) yielding the area-under-the-curve of .941 (P < .001). MwMR correlated negatively with the drop in systolic blood pressure (SBP) during AFTs {Pearson-coefficient (-).565, P = .002}. Mean MwMR in patients with abnormal-AFTs was significantly lower than patients with borderline-AFTs (1.39 ± .12 vs 1.55 ± .10; P = .002). 9/20 patients with abnormal-AFTs showed functional worsening during follow-up, compared to 2/8 with borderline-AFTs. CONCLUSION: Single tracer, single session imaging of striatal and cardiac sympathetic dysfunction in patients with advanced IPD is feasible with use of 18F-FDOPA. Significantly reduced 18F-FDOPA uptake is seen in the myocardium of the IPD patients with sympathetic dysfunction.


Assuntos
Cardiopatias , Disautonomias Primárias , Idoso , Di-Hidroxifenilalanina/análogos & derivados , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
20.
J Nucl Med ; 63(3): 384-388, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34272321

RESUMO

Our objective was to assess the value of 68Ga-DOTATOC and carbidopa-assisted 18F-fluorodihydroxyphenylalanine (18F-DOPA) in 21 hypoglycemic patients. Methods: All patients who underwent 68Ga-DOTATOC or carbidopa-assisted 18F-DOPA PET/CT for suspicion of insulinoma from January 2019 to January 2021 were retrospectively analyzed. A final diagnosis of insulinoma was determined by pathologic reports or consensus. Results: During the study period, 21 patients underwent both 68Ga-DOTATOC and 18F-DOPA PET/CT. A final diagnosis of insulin-secreting tumor was reached in 12 cases, including 11 insulinomas and 1 small mixed neuroendocrine/nonneuroendocrine neoplasm. 18F-DOPA and 68Ga-DOTATOC PET/CT were positive in 5 (45%) and 7 (64%) of 11 cases, respectively, with 4 concordant positive findings. Moreover, 1 insulinoma was visualized exclusively by 18F-DOPA PET/CT and 3 by 68Ga-DOTATOC PET/CT only. 18F-DOPA and 68Ga-DOTATOC PET/CT were falsely positive in 1 nonfunctioning pancreatic neuroendocrine tumor. Conclusion: When 68Ga-exendin-4 is not available, 68Ga-somatostatin receptor PET/CT should be the first choice for insulinoma functional imaging.


Assuntos
Insulinoma , Tumores Neuroendócrinos , Compostos Organometálicos , Neoplasias Pancreáticas , Carbidopa , Di-Hidroxifenilalanina/análogos & derivados , Radioisótopos de Gálio , Humanos , Insulinoma/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Octreotida/análogos & derivados , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos
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