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1.
J Nucl Med ; 65(7): 1013-1020, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38844361

RESUMO

This study aimed to compare the efficacy of [18F]F-choline PET/CT with conventional imaging for staging and managing intermediate- to high-risk prostate cancer (PCa). The primary objective was to assess the ability of PET/CT with [18F]F-choline to identify lymph node and systemic involvement during initial staging. Secondary objectives included evaluating the impact of [18F]F-choline PET/CT on unnecessary local treatments and assessing the safety of [18F]F-choline agents. Additionally, the study aimed to analyze recurrence-free survival and overall survival 5 y after randomization. Methods: A prospective controlled, open, randomized multicenter phase III trial involving 7 Italian centers was conducted. Eligible patients with intermediate- to high-risk PCa were randomized in a 1:1 ratio. Two groups were formed: one undergoing conventional imaging (abdominopelvic contrast-enhanced CT and bone scanning) and the other receiving conventional imaging plus [18F]F-choline PET/CT. The study was terminated prematurely; however, all the endpoints were thoroughly analyzed and enriched. Results: Between February 2016 and December 2020, 256 patients were randomly assigned. In total, 236 patients (117 in the control arm and 119 in the experimental arm) were considered for the final assessment. In the experimental arm, the sensitivity for lymph node metastases, determined by final pathology and serial prostate-specific antigen evaluations, was higher than in the control arm (77.78% vs. 28.57% and 65.62% vs. 17.65%, respectively). The [18F]F-choline was tolerated well. The use of [18F]F-choline PET/CT resulted in an approximately 8% reduction in unnecessary extended lymphadenectomy compared with contrast-enhanced CT. Additionally, [18F]F-choline PET/CT had a marginal impact on 5-y overall survival, contributing to a 4% increase in survival rates. Conclusion: In the initial staging of PCa, [18F]F-choline PET/CT exhibited diagnostic performance superior to that of conventional imaging for detecting metastases. [18F]F-choline PET/CT reduced the rate of unnecessary extensive lymphadenectomy by up to 8%. These findings support the consideration of discontinuing conventional imaging for staging PCa.


Assuntos
Colina , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Colina/análogos & derivados , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Radioisótopos de Flúor
2.
Nucl Med Commun ; 45(9): 796-803, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38832429

RESUMO

OBJECTIVE: This study compared the radiomic features and quantitative biomarkers of 18 F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18 F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. METHODS: A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUV mean , PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. RESULTS: Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUV max value was significantly higher for 18 F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P  < 0.001). There were statistically significant differences in median SUV mean , TL-PSMA/FCH, and PSMA/FCH-TV between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P  < 0.001). The correlation between SUV mean /SUV max and PSA level was moderate, both for 18 F-PSMA ( r  = 0.44, P  < 0.001; r  = 0.44, P  < 0.001) and FCH ( r  = 0.35, P  < 0.001; r  = 0.41, P  < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18 F-PSMA ( r  = 0.56, P  < 0.001; r  = 0.57, P  < 0.001) and FCH ( r  = 0.49, P  < 0.001; r  = 0.51, P  < 0.001). While patients who received hormone therapy showed higher median SUV max values for both radiotracers compared with those who did not, the difference was statistically significant only for 18 F-PSMA ( P  < 0.05). CONCLUSION: Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18 F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.


Assuntos
Colina , Niacinamida , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Colina/análogos & derivados , Idoso , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Recidiva , Oligopeptídeos , Biomarcadores Tumorais/metabolismo , Idoso de 80 Anos ou mais , Antígeno Prostático Específico/metabolismo , Antígeno Prostático Específico/sangue , Radiômica
3.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891947

RESUMO

Esterquats constitute a unique group of quaternary ammonium salts (QASs) that contain an ester bond in the structure of the cation. Despite the numerous advantages of this class of compounds, only two mini-reviews discuss the subject of esterquats: the first one (2007) briefly summarizes their types, synthesis, and structural elements required for a beneficial environmental profile and only briefly covers their applications whereas the second one only reviews the stability of selected betaine-type esterquats in aqueous solutions. The rationale for writing this review is to critically reevaluate the relevant literature and provide others with a "state-of-the-art" snapshot of choline-type esterquats and betaine-type esterquats. Hence, the first part of this survey thoroughly summarizes the most important scientific reports demonstrating effective synthesis routes leading to the formation of both types of esterquats. In the second section, the susceptibility of esterquats to hydrolysis is explained, and the influence of various factors, such as the pH, the degree of salinity, or the temperature of the solution, was subjected to thorough analysis that includes quantitative components. The next two sections refer to various aspects associated with the ecotoxicity of esterquats. Consequently, their biodegradation and toxic effects on microorganisms are extensively analyzed as crucial factors that can affect their commercialization. Then, the reported applications of esterquats are briefly discussed, including the functionalization of macromolecules, such as cotton fabric as well as their successful utilization on a commercial scale. The last section demonstrates the most essential conclusions and reported drawbacks that allow us to elucidate future recommendations regarding the development of these promising chemicals.


Assuntos
Betaína , Cátions , Colina , Betaína/química , Betaína/análogos & derivados , Colina/química , Colina/análogos & derivados , Cátions/química , Ésteres/química , Compostos de Amônio Quaternário/química , Humanos
4.
Clin Nucl Med ; 49(9): 860-861, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38915157

RESUMO

ABSTRACT: Collateral circulation is often secondary to a regional thrombosis. This phenomenon can lead to the detection of misleading bone lesions on imaging and is a well-known source of false-positives. Here, we present 2 different tracers PET/CT images, 18 F-FDG and 18 F-choline, with collateral circulation but without obvious thrombosis. Both cases displayed bone uptake, which mimicked metastasis. However, clinical follow-up ruled out metastasis and revealed false-positive bone lesions related to collateral circulation, even in the lack of acute or chronic underlying thrombotic processes.


Assuntos
Circulação Colateral , Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Trombose , Humanos , Trombose/diagnóstico por imagem , Trombose/fisiopatologia , Reações Falso-Positivas , Masculino , Traçadores Radioativos , Pessoa de Meia-Idade , Feminino , Colina/análogos & derivados , Osso e Ossos/diagnóstico por imagem
5.
J Nucl Med ; 65(8): 1202-1209, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38906557

RESUMO

Metastasis-directed therapy (MDT) has been tested in clinical trials as a treatment option for oligorecurrent prostate cancer (PCa). However, there is an ongoing debate regarding the impact of using different imaging techniques interchangeably for defining lesions and guiding MDT within clinical trials. Methods: We retrospectively identified oligorecurrent PCa patients who had 5 or fewer nodal, bone, or visceral metastases detected by choline or prostate-specific membrane antigen (PSMA) PET/CT and who underwent MDT stereotactic body radiotherapy with or without systemic therapy in 8 tertiary-level cancer centers. Imaging-guided MDT was assessed as progression-free survival (PFS), time to systemic treatment change due to polymetastatic conversion (PFS2), and overall survival predictor. Propensity score matching was performed to account for clinical differences between groups. Results: Of 402 patients, 232 (57.7%) and 170 (42.3%) underwent MDT guided by [18F]fluorocholine and PSMA PET/CT, respectively. After propensity score matching, patients treated with PSMA PET/CT-guided MDT demonstrated longer PFS (hazard ratio [HR], 0.49 [95% CI, 0.36-0.67]; P < 0.0001), PFS2 (HR, 0.42 [95% CI, 0.28-0.63]; P < 0.0001), and overall survival (HR, 0.39 [95% CI, 0.15-0.99]; P < 0.05) than those treated with choline PET/CT-guided MDT. Additionally, we matched patients who underwent [68Ga]Ga-PSMA-11 versus [18F]F-PSMA-1007 PET/CT, observing longer PFS and PFS2 in the former subgroup (PFS: HR, 0.51 [95% CI, 0.26-1.00]; P < 0.05; PFS2: HR, 0.24 [95% CI, 0.09-0.60]; P < 0.05). Conclusion: Diverse imaging methods may influence outcomes in oligorecurrent PCa patients undergoing MDT. However, prospective, head-to-head studies, ideally incorporating a randomized design, are necessary to provide definitive evidence and facilitate the practical application of these findings.


Assuntos
Metástase Neoplásica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Pessoa de Meia-Idade , Recidiva , Radiocirurgia , Colina/análogos & derivados , Idoso de 80 Anos ou mais
6.
Phys Chem Chem Phys ; 26(22): 16218-16233, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38804505

RESUMO

The micellization of choline-based anionic surface-active ionic liquids (SAILs) having lauroyl sarcosinate [Sar]-, dodecylsulfate [DS]-, and deoxycholate [Doc]- as counter-ions was investigated in an aqueous medium. Density functional theory (DFT) was employed to investigate the net interactional energy (Enet), extent of non-covalent interactions, and band gap of the choline-based SAILs. The critical micelle concentration (cmc) along with various parameters related to the surface adsorption, counter-ion binding (ß), and polarity of the cores of the micelles were deduced employing surface tension measurements, conductometric titrations and fluorescence spectroscopy, respectively. A dynamic light scattering (DLS) system equipped with zeta-potential measurement set-up and small-angle neutron scattering (SANS) were used to predict the size, zeta-potential, and morphology, respectively, of the formed micelles. Thermodynamic parameters such as standard Gibb's free energy and standard enthalpy change of micellization were calculated using isothermal titration calorimetry (ITC). Upon comparing with sodium salt analogues, it was established that the micellization was predominantly governed by the extent of hydration of [Cho]+, the head groups of the respective anions, and the degree of counter-ion binding (ß). Considering the concentration dependence of the enzyme-SAIL interactions, aqueous solutions of the synthesized SAILs at two different concentrations (below and above the cmc) were utilized as the medium for testing the enzymatic activity of cellulase. The activity of cellulase was found to be ∼7- to ∼13-fold higher compared to that observed in buffers in monomeric solutions of the SAILs and followed the order: [Cho][Sar] > [Cho][DS] > [Cho][Doc]. In the micellar solution, a ∼4- to 5-fold increase in enzymatic activity was observed.


Assuntos
Celulase , Colina , Líquidos Iônicos , Micelas , Água , Líquidos Iônicos/química , Colina/química , Colina/análogos & derivados , Celulase/química , Celulase/metabolismo , Água/química , Termodinâmica , Tensoativos/química , Teoria da Densidade Funcional
7.
Neuroimage Clin ; 42: 103616, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38763039

RESUMO

PURPOSE: The main objective was to characterize the tracer uptake kinetics of [18F]fluoromethylcholine ([18F]F-CHO) in high-grade gliomas (HGG) through a full PET kinetic modeling approach. Secondarily, we aimed to explore the relationship between the PET uptake measures and the HGG molecular features. MATERIALS AND METHODS: Twenty-four patients with a suspected diagnosis of HGG were prospectively included. They underwent a dynamic brain [18F]F-CHO-PET/CT, from which a tumoral time-activity curve was extracted. The plasma input function was obtained through arterial blood sampling with metabolite correction. These data were fitted to 1- and 2-tissue-compartment models, the best of which was selected through the Akaike information criterion. We assessed the correlation between the kinetic parameters and the conventional static PET metrics (SUVmax, SUVmean and tumor-to-background ratio TBR). We explored the association between the [18F]F-CHO-PET quantitative parameters and relevant molecular biomarkers in HGG. RESULTS: Tumoral time-activity curves in all patients showed a rapid rise of [18F]F-CHO uptake followed by a plateau-like shape. Best fits were obtained with near-irreversible 2-tissue-compartment models. The perfusion-transport constant K1 and the net influx rate Ki showed strong correlation with SUVmax (r = 0.808-0.861), SUVmean (r = 0.794-0.851) and TBR (r = 0.643-0.784), p < 0.002. HGG was confirmed in 21 patients, of which those with methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene promoter showed higher mean Ki (p = 0.020), K1 (p = 0.025) and TBR (p = 0.001) than the unmethylated ones. CONCLUSION: [18F]F-CHO uptake kinetics in HGG is best explained by a 2-tissue-compartment model. The conventional static [18F]F-CHO-PET measures have been validated against the perfusion-transport constant (K1) and the net influx rate (Ki) derived from kinetic modeling. A relationship between [18F]F-CHO uptake rate and MGMT methylation is suggested but needs further confirmation.


Assuntos
Neoplasias Encefálicas , Colina , Glioma , Humanos , Glioma/diagnóstico por imagem , Glioma/metabolismo , Pessoa de Meia-Idade , Masculino , Feminino , Colina/análogos & derivados , Colina/metabolismo , Colina/farmacocinética , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Adulto , Idoso , Tomografia por Emissão de Pósitrons/métodos , Cinética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/farmacocinética , Estudos Prospectivos , Gradação de Tumores
8.
Am J Otolaryngol ; 45(4): 104315, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38701728

RESUMO

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.


Assuntos
Colina , Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Tomografia Computadorizada de Emissão de Fóton Único , Humanos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Colina/análogos & derivados , Idoso , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/complicações , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adenoma/diagnóstico por imagem , Adenoma/cirurgia , Tomografia por Emissão de Pósitrons/métodos , Adulto , Valor Preditivo dos Testes , Ultrassonografia/métodos , Sensibilidade e Especificidade , Radioisótopos de Flúor , Compostos Radiofarmacêuticos
9.
Clin Nucl Med ; 49(6): 559-560, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557413

RESUMO

ABSTRACT: A 56-year-old man with thoracal mass suspected of solitary plasmacytoma was referred for 18 F-FDG PET-CT scan. His PET-CT revealed FDG-avid rib mass and cervical lesion at level 2. He also underwent 18 F-fluorocholine (FCH) PET-CT to evaluate possible metastatic spread of the disease. FCH PET-CT showed increased uptake at the rib mass, while the cervical lesion was not FCH-avid. Biopsies confirmed rib lesion was a solitary plasmacytoma; however, the cervical lesion was an amyloid deposited lymph node. This case showed FCH PET-CT is a valuable companion of FDG scan for the evaluation of plasma cell dyscrasias with a better specificity.


Assuntos
Colina/análogos & derivados , Fluordesoxiglucose F18 , Linfadenopatia , Plasmocitoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Pessoa de Meia-Idade , Plasmocitoma/diagnóstico por imagem , Plasmocitoma/patologia , Linfadenopatia/diagnóstico por imagem , Amiloide/metabolismo
11.
J Pediatr Endocrinol Metab ; 37(6): 580-584, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38661069

RESUMO

OBJECTIVES: The most common cause of primary hyperparathyroidism (PPH) in children is a parathyroid adenoma. Among this population, PPH exhibits higher levels of morbidity, severity and target organ involvement compared to adults. When there is suspicion of PPH, cervical ultrasound and 99mTc-sestamibi SPECT/CT are the imaging test traditionally indicated. Among adults, the use of [18F]fluorocholine PET/CT has shown a higher sensitivity than ultrasound and [99mTc]sestamibi SPECT/CT, leading to an expanding adoption in recent years. However, its role in paediatrics has not been clearly defined yet. CASE PRESENTATION: The patient is an adolescent female aged 13 years presented with lithiasis. The analytical study revealed elevated PTH, hipovitaminosis D, hypercalcaemia and hypophosphataemia. Due to the suspicion of PPH, cervical ultrasound and 99mTc-sestamibi SPECT/C were performed, failing to identify hyperfunctioning parathyroid glands. We proceeded to carry out a [18F]fluorocholine PET/CT where a hypermetabolic nodular image was identified, compatible with a hyperfunctioning parathyroid adenoma. The patient underwent surgery, resulting in the normalisation of PTH levels. Pathological anatomy confirmed the presence of a parathyroid adenoma. CONCLUSIONS: In cases where conventional imaging tests yield negative results or discrepancies, we suggest the possibility of the use of [18F]fluorocholine PET/CT for the detection of hyperfunctioning parathyroid adenomas.


Assuntos
Colina , Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Adolescente , Hiperparatireoidismo Primário/diagnóstico por imagem , Colina/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/patologia , Compostos Radiofarmacêuticos , Prognóstico , Adenoma/diagnóstico por imagem , Radioisótopos de Flúor
12.
Exp Clin Endocrinol Diabetes ; 132(4): 216-220, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38320618

RESUMO

OBJECTIVE: This study aimed to assess the diagnostic performance of 99mTc-sestamibi SPECT/CT and 18F-choline PET/CT in detecting hyperfunctioning parathyroid glands in patients undergoing surgery for primary hyperparathyroidism (PHPT). METHODS: A retrospective analysis was conducted on patients who underwent PHPT-related surgery between April 2019 and May 2022. The study focused on patients undergoing either 99mTc-sestamibi SPECT/CT (81 patients) or 18F-choline PET/CT (33 patients) scans before surgery to pinpoint hyperfunctioning parathyroid gland(s). In the majority of patients, 18F-choline PET/CT was performed after negative or inconclusive findings on 99mTc-sestamibi SPECT/CT. Pathohistological reports were utilized as the reference standard for evaluating the accuracy of the imaging findings. RESULTS: The study encompassed 83 patients (70 females, 84.3%) with an average age of 57.2 years (24-80 years). The pathohistological analysis identified a total of 98 glands. In a per-lesion analysis, the detection rate of 99mTc-sestamibi SPECT/CT was 57% (95% CI 45.3-68.1), while the detection rate of 18F-choline PET/CT was 90.3% (95% CI 74.3-98.0). CONCLUSION: The results of our study showed the significant usefulness of 18F-choline PET/CT in patients with negative or inconclusive results of 99mTc-sestamibi SPECT/CT in accurately locating hyperfunctioning parathyroid glands in PHPT patients.


Assuntos
Colina/análogos & derivados , Hiperparatireoidismo Primário , Glândulas Paratireoides , Feminino , Humanos , Pessoa de Meia-Idade , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tecnécio Tc 99m Sestamibi , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton Único
13.
Phytomedicine ; 126: 155200, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38387273

RESUMO

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCß3 axis acting as a core node of RAAS. PLCß3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development. PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCß3 axis and its molecular mechanism. STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCß3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms. METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods. RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCß3. The underlying mechanism for blocking the Gαq-PLCß3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCß3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system. CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCß3 interaction blockade by targeting the PLCß3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs.


Assuntos
Doenças Cardiovasculares , Colina/análogos & derivados , Hiperaldosteronismo , Hipertensão , Animais , Doenças Cardiovasculares/tratamento farmacológico , Motivos EF Hand , Hipertensão/tratamento farmacológico
15.
Actas Urol Esp (Engl Ed) ; 48(4): 328-334, 2024 May.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38159802

RESUMO

INTRODUCTION AND OBJECTIVE: Next-generation imaging (NGI) tests, such as choline PET/CT and PSMA PET, have shown to increase sensitivity in the detection of nodal and metastatic disease in prostate cancer. However, their use implies an increase in diagnostic costs compared to conventional imaging (CI) tests such as CT and bone scan. The aim of our study was to determine which diagnostic pathway is more cost-effective in high-risk prostate cancer. MATERIAL AND METHOD: Cost-effectiveness analysis of the available imaging tests (CI, Choline/PSMA PET) for the staging of high-risk prostate cancer. Sensitivity and specificity were estimated based on published evidence, and costs were collected from the Management Department. In order to carry out a cost-effectiveness analysis, five diagnostic pathways were proposed estimating the accurate diagnoses. RESULTS: PSMA PET was the most accurate diagnostic option. The CI diagnostic workup was the most economical and CI+PSMA the most expensive. Analyzing the diagnostic cost-effectiveness ratio, CI+PSMA proved to be the most expensive (€5627.30 per correct diagnosis) followed by PET PSMA (€4987.11), choline (€4599.84) and CI (€4444.22). CONCLUSIONS: PSMA PET is the most accurate strategy in staging distant disease in patients with high-risk prostate cancer. Radiotracer uptake tests such as CI have been shown to be the most cost-effective option, followed by choline and PSMA.


Assuntos
Análise Custo-Benefício , Estadiamento de Neoplasias , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/economia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Colina/análogos & derivados , Custos e Análise de Custo , Medição de Risco
16.
J Clin Densitom ; 27(1): 101464, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38150889

RESUMO

INTRODUCTION: Measurement of bone mineral density (BMD) with quantitative CT (QCT) carries several advantages over other densitometric techniques, including superior assessment of the spine. As most QCT studies evaluated the lumbar spine, measurements of the thoracic spine are limited. We performed QCT analysis of the thoracic spine in a cohort of patients with primary hyperparathyroidism. MATERIALS AND METHODS: This study was a retrospective QCT analysis of the thoracic spine on 18F-fluorocholine PET/CT scans in patients with primary hyperparathyroidism patients between March 2018 and December 2022. Correlations between QCT-derived BMD or Hounsfield units (HU) and demographic data, laboratory parameters, results from histopathological examination after parathyroidectomy and results of DXA imaging were analyzed, when available. RESULTS: In 189 patients, mean QCT-derived BMD at the thoracic spine was 85.6 mg/cm3. Results from recent DXA were available in 122 patients. Mean thoracic QCT-derived BMD and HU were significantly correlated with DXA-derived BMD in lumbar spine, total hip and femoral neck and with the lowest T-score at DXA imaging. Only weak correlations were found with BMI or 18F-fluorocholine uptake, while no significant correlations were found with adenoma weight, PTH or calcium levels. CONCLUSION: Our study confirms correlation between QCT-derived BMD in the thoracic spine with age and DXA-derived BMD measurements within a population of patients with primary hyperparathyroidism. Establishment of reference BMD values for individual thoracic vertebrae, may allow direct osteoporosis classification on thoracic CT imaging.


Assuntos
Densidade Óssea , Colina/análogos & derivados , Hiperparatireoidismo Primário , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Retrospectivos , Hiperparatireoidismo Primário/diagnóstico por imagem , Absorciometria de Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Vértebras Lombares/diagnóstico por imagem
19.
Actual. osteol ; 15(1): 11-19, ene. abr. 2019. tab., ilus.
Artigo em Espanhol | LILACS | ID: biblio-1048549

RESUMO

El hiperparatiroidismo persistente/recurrente representa un desafío en la localización del tejido paratiroideo hiperfuncionante. En esta subpoblación, los métodos convencionales ofrecen un menor rédito diagnóstico. La 18F-colina PET/TC podría ser una buena alternativa dada su mejor resolución espacial, capacidad de detectar glándulas ectópicas y la conjunción de la imagen molecular y anatómica. Sin embargo, la evidencia en este subgrupo de pacientes es escasa. Objetivo: evaluar la utilidad de la 18F-colina PET/TC como método de localización en el hiperparatiroidismo persistente o recurrente. Materiales y métodos: se analizaron los pacientes con 18F-colina PET/TC para hiperparatiroidismo entre diciembre de 2015 y enero de 2018 en un centro terciario de alto volumen. Se analizaron el número de lesiones, su localización, tamaño y el Standard Uptake Value máximo (SUV max) en las imágenes tempranas y tardías. Se compararon los resultados con los métodos convencionales. Resultados: 7 de 15 pacientes habían sido operados previamente (persistentes/recurrentes). La 18F-colina PET/TC detectó 6/7 casos (83,33%), la ecografía cervical 1/4 (25%) y el SPECT de paratiroides y la resonancia nuclear magnética 2/5 (40%). El SUV max obtenido fue variable, en la mitad de los casos a los 10 minutos y en los restantes a la hora; el tamaño promedio de las lesiones fue 8,61 mm (6-12 mm). Conclusiones: la 18F-colina PET/TC muestra una alta tasa de detección en los pacientes con hiperparatiroidismo persistente/recurrente. La combinación del comportamiento biológico del PET con los hallazgos morfológicos aportados por la TC con contraste endovenoso le ofrecería ventajas sobre otros estudios que podrían posicionarlo como método de primera línea en esta subpoblación. (AU)


Persistent or recurrent hyperparathyroidism represents a challenge regarding the localization of the hyper-functioning parathyroid tissue. In this subpopulation of hyperpharathyroid patients, conventional methods have a low diagnostic yield. The 18F-choline PET /CT could be a good alternative given its better spatial resolution, ability to detect ectopic glands, and the conjunction of the molecular and anatomical image. However, the evidence in this subgroup of patients is limited. Objective: to evaluate the utility of 18F-choline PET/ CT as a localization method in persistent or recurrent hyperparathyroidism. Materials and methods: patients with 18F-choline PET / CT for hyperparathyroidism between December 2015 and January 2018 in a high-volume tertiary center were included. The number of lesions, and their location, size, and maximum Standard Uptake Value (SUV) in the early and late images were analyzed. The results were compared to conventional methods. Results: 7 of 15 patients had been previously operated (persistent/recurrent). 18F-choline PET / CT detected 6/7 cases (83,33%), cervical ultrasound 1/4 (25%) and parathyroid SPECT and magnetic resonance 2/5 (40%). The maximum SUV was variable, one half at 10 minutes and the other half at 60 minutes; the average size of the lesions was 8.61 mm (6-12 mm). Conclusions: 18F-Choline PET / CT shows a high detection rate in patients with persistent / recurrent hyperparathyroidism. The combination of the biological behavior of PET with the morphological findings provided by CT with intravenous contrast would offer advantages over other studies that could position it as a first line method in this subpopulation. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Hiperparatireoidismo Primário/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Recidiva , Vitamina D/sangue , Espectroscopia de Ressonância Magnética/estatística & dados numéricos , Tomografia Computadorizada de Emissão de Fóton Único/estatística & dados numéricos , Colina/análogos & derivados , Ultrassonografia/estatística & dados numéricos , Fluordesoxiglucose F18 , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/complicações , Hiperparatireoidismo Primário/etiologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Metionina/análogos & derivados
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