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1.
PNAS Nexus ; 3(7): pgae274, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39045017

RESUMEN

Refractory bricks are bricks that can withstand high temperatures without damage to their structures. They have been used to insulate kilns, furnaces, and other hot enclosures for thousands of years. Firebricks are refractory bricks that can, with one composition, store heat, and with another, insulate the firebricks that store the heat. Because firebricks are made from common materials, the cost per kilowatt-hour-thermal of a firebrick storage system is less than one-tenth the cost per kilowatt-hour-electricity of a battery system. It has thus been hypothesized that using excess renewable electricity to produce and store industrial process heat in firebricks can provide a low-cost source of continuous heat for industry. Here, it is hypothesized further that, upon a transition to 100% clean, renewable energy worldwide, using firebricks to store industrial process heat can reduce electricity generator, electricity storage, and low-temperature heat storage needs, thereby reducing overall energy cost. Both hypotheses are tested across 149 countries combined into 29 world regions. Results suggest, relative to a base case with no firebricks, using firebricks may reduce, among all 149 countries, 2050 battery capacity by ∼14.5%, annual hydrogen production for grid electricity by ∼31%, underground low-temperature heat storage capacity by ∼27.3%; onshore wind nameplate capacity by ∼1.2%, land needs by ∼0.4%, and overall annual energy cost by ∼1.8%. In sum, the use of firebricks for storing industrial process heat appears to be a remarkable tool in reducing the cost of transitioning to clean, renewable energy across all energy sectors.

2.
Am J Ind Med ; 67(4): 334-340, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38316635

RESUMEN

BACKGROUND: Hybrid immunity, from COVID-19 vaccination followed by SARS-CoV-2 infection acquired after its Omicron variant began predominating, has provided greater protection than vaccination alone against subsequent infection over 1-3 months of observation. Its longer-term protection is unknown. METHODS: We conducted a retrospective cohort study of COVID-19 case incidence among healthcare personnel (HCP) mandated to be vaccinated and report on COVID-19-associated symptoms, high-risk exposures, or known-positive test results to an employee health hotline. We compared cases with hybrid immunity, defined as incident COVID-19 during the first 6 weeks of Omicron-variant predominance (run-in period), to those with immunity from vaccination alone during the run-in period. Time until COVID-19 infection over 13 subsequent months (observation period) was analyzed by standard survival analysis. RESULTS: Of 5867 employees, 641 (10.9%, 95% confidence interval [CI]: 10.1%-11.8%) acquired hybrid immunity during the run-in period. Of these, 104 (16.2%, 95% CI: 13.5%-19.3%) experienced new SARS-CoV-2 infection during the 13-month observation period, compared to 2177 (41.7%, 95% CI: 40.3%-43.0%) of the 5226 HCP without hybrid immunity. Time until incident infection was shorter among the latter (hazard ratio: 3.09, 95% CI: 2.54-3.78). CONCLUSIONS: In a cohort of vaccinated employees, Omicron-era acquired SARS-CoV-2 hybrid immunity was associated with significantly lower risk of subsequent infection over more than a year of observation-a time period far longer than previously reported and during which three, progressively more resistant, Omicron subvariants became predominant. These findings can inform institutional policy and planning for future COVID-19 additional vaccine dosing requirements for employees, for surveillance programs, and for risk modification efforts.


Asunto(s)
COVID-19 , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , SARS-CoV-2 , Pandemias , Estudios Retrospectivos , Inmunidad Adaptativa
3.
iScience ; 27(2): 108988, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38352224

RESUMEN

Grids require electricity storage. Two emerging storage technologies are battery storage (BS) and green hydrogen storage (GHS) (hydrogen produced and compressed with clean-renewable electricity, stored, then returned to electricity with a fuel cell). An important question is whether GHS alone decreases system cost versus BS alone or BS + GHS. Here, energy costs are modeled in 145 countries grouped into 24 regions. Existing conventional hydropower (CH) storage is used along with new BS and/or GHS. A method is developed to treat CH for both baseload and peaking power. In four regions, only CH is needed. In five, CH + BS is the lowest cost. Otherwise, CH + BS + GHS is the lowest cost. CH + GHS is never the lowest cost. A metric helps estimate whether combining GHS with BS reduces cost. In most regions, merging (versus separating) grid and non-grid hydrogen infrastructure reduces cost. In sum, worldwide grid stability may be possible with CH + BS or CH + BS + GHS. Results are subject to uncertainties.

4.
PLoS One ; 18(11): e0294564, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38011131

RESUMEN

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease prone to widespread metastatic dissemination and characterized by a desmoplastic stroma that contributes to poor outcomes. Fibroblast activation protein (FAP)-expressing Cancer-Associated Fibroblasts (CAFs) are crucial components of the tumor stroma, influencing carcinogenesis, fibrosis, tumor growth, metastases, and treatment resistance. Non-invasive tools to profile CAF identity and function are essential for overcoming CAF-mediated therapy resistance, developing innovative targeted therapies, and improved patient outcomes. We present the design of a multicenter phase 2 study (clinicaltrials.gov identifier NCT05262855) of [68Ga]FAPI-46 PET to image FAP-expressing CAFs in resectable or borderline resectable PDAC. METHODS: We will enroll up to 60 adult treatment-naïve patients with confirmed PDAC. These patients will be eligible for curative surgical resection, either without prior treatment (Cohort 1) or after neoadjuvant therapy (NAT) (Cohort 2). A baseline PET scan will be conducted from the vertex to mid-thighs approximately 15 minutes after administering 5 mCi (±2) of [68Ga]FAPI-46 intravenously. Cohort 2 patients will undergo an additional PET after completing NAT but before surgery. Histopathology and FAP immunohistochemistry (IHC) of initial diagnostic biopsy and resected tumor samples will serve as the truth standards. Primary objective is to assess the sensitivity, specificity, and accuracy of [68Ga]FAPI-46 PET for detecting FAP-expressing CAFs. Secondary objectives will assess predictive values and safety profile validation. Exploratory objectives are comparison of diagnostic performance of [68Ga]FAPI-46 PET to standard-of-care imaging, and comparison of pre- versus post-NAT [68Ga]FAPI-46 PET in Cohort 2. CONCLUSION: To facilitate the clinical translation of [68Ga]FAPI-46 in PDAC, the current study seeks to implement a coherent strategy to mitigate risks and increase the probability of meeting FDA requirements and stakeholder expectations. The findings from this study could potentially serve as a foundation for a New Drug Application to the FDA. TRIAL REGISTRATION: @ClinicalTrials.gov identifier NCT05262855.


Asunto(s)
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adulto , Humanos , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Radioisótopos de Galio , Adenocarcinoma/tratamiento farmacológico , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/tratamiento farmacológico , Tomografía de Emisión de Positrones , Fibroblastos/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fluorodesoxiglucosa F18/uso terapéutico , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como Asunto , Neoplasias Pancreáticas
5.
Environ Sci Technol ; 57(44): 16843-16850, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37882448

RESUMEN

An important issue today is whether gasoline vehicles should be replaced by flex-fuel vehicles (FFVs) that use ethanol-gasoline blends (e.g., E85), where some carbon dioxide (CO2) from ethanol's production is captured and piped, or battery-electric vehicles (BEVs) powered by wind or solar. This paper compares the options in a case study. It evaluates a proposal to capture fermentation CO2 from 34 ethanol refineries in 5 U.S. states and build an elaborate pipeline to transport the CO2 to an underground storage site. This "ethanol plan" is compared with building wind farms at the same cost to provide electricity for BEVs ("wind plan A"). Compared with the ethanol plan, wind plan A may reduce 2.4-4 times the CO2, save drivers in the five states $40-$66 billion (USD 2023) over 30 years even when BEVs initially cost $21,700 more than FFVs, require 1/400,000th the land footprint and 1/10th-1/20th the spacing area, and decrease air pollution. Even building wind to replace coal ("wind plan B") may avoid 1.5-2.5 times the CO2 as the ethanol plan. Thus, ethanol with carbon capture appears to be an opportunity cost that may damage climate and air quality, occupy land, and saddle consumers with high fuel costs for decades.


Asunto(s)
Fuentes Generadoras de Energía , Gasolina , Gasolina/análisis , Etanol/análisis , Dióxido de Carbono/análisis , Viento , Electricidad , Emisiones de Vehículos/análisis , Vehículos a Motor
6.
J Occup Environ Med ; 65(2): 125-127, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36240750

RESUMEN

OBJECTIVE: Most health care personnel (HCP) reporting symptoms consistent with COVID-19 illness are assessed by high-accuracy SARS-CoV-2 assays performed in clinical laboratories, but the results of such assays typically are not available until the following day. METHODS: This is an observational study over 16 weeks of a rapid nucleic acid amplification test (NAAT) performed at point of contact. The benchmark for comparison was a simultaneously obtained specimen assayed by a routine NAAT assay performed in a clinical laboratory. RESULTS: There were 577 paired rapid and routine NAAT results. Rapid test positive predictive value was 90.0% (95% confidence interval = 88.8%-91.2%), and negative predictive value was 95.2% (95% confidence interval = 93.5%-96.9%). The rapid test avoided an estimated 160 to 184 lost work shifts over 4 months. CONCLUSIONS: A rapid NAAT test-based strategy proved effective in safely clearing symptomatic employees without infection for earlier return to work.


Asunto(s)
COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Valor Predictivo de las Pruebas , Técnicas de Amplificación de Ácido Nucleico , Atención a la Salud , Sensibilidad y Especificidad
7.
Am J Psychiatry ; 179(7): 490-499, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35582785

RESUMEN

OBJECTIVE: Altered glutamatergic neurotransmission is implicated in the pathogenesis of major depressive disorder. AXS-05 (dextromethorphan-bupropion) is an oral NMDA receptor antagonist and sigma-1 receptor agonist, which utilizes inhibition of CYP2D6 to increase its bioavailability. This phase 2 trial assessed the efficacy and safety of dextromethorphan-bupropion in the treatment of major depressive disorder. METHODS: This randomized, double-blind, multicenter, parallel-group trial evaluated dextromethorphan-bupropion versus the active comparator sustained-release bupropion in patients 18-65 years old with a diagnosis of major depressive disorder of moderate or greater severity. Patients were randomly assigned to receive either dextromethorphan-bupropion (45 mg/105 mg tablet) or bupropion (105 mg tablet), once daily for the first 3 days and twice daily thereafter, for a total of 6 weeks. The primary endpoint was overall treatment effect on Montgomery-Åsberg Depression Rating Scale (MADRS) score (average of the change from baseline for weeks 1-6), assessed in all randomized patients whose diagnosis and severity were confirmed by an independent assessor and who received at least one dose of study medication and had at least one postbaseline assessment. RESULTS: Of 97 patients randomized, 17 did not have a confirmed diagnosis and severity based on the independent assessment, resulting in 80 patients in the efficacy population (dextromethorphan-bupropion, N=43; bupropion, N=37). The mean change from baseline in MADRS score over weeks 1-6 (overall treatment effect) was significantly greater with dextromethorphan-bupropion than with bupropion (-13.7 points vs. -8.8 points; least-squares mean difference=-4.9; 95% CI=-3.1, -6.8). MADRS score change with dextromethorphan-bupropion was significantly greater than with bupropion at week 2 and every time point thereafter (week 6: -17.3 vs. -12.1 points; least-squares mean difference=-5.2, 95% CI=-1.1, -9.3). Remission rates were significantly greater with dextromethorphan-bupropion at week 2 and every time point thereafter (week 6: 46.5% vs. 16.2%; least-squares mean difference=30.3%, 95% CI=11.2, 49.4). Response rates (≥50% decrease in MADRS score from baseline) at week 6 were 60.5% with dextromethorphan-bupropion and 40.5% with bupropion (least-squares mean difference=19.9%, 95% CI=-1.6, 41). Most secondary outcomes favored dextromethorphan-bupropion. The most common adverse events with dextromethorphan-bupropion were dizziness, nausea, dry mouth, decreased appetite, and anxiety. Dextromethorphan-bupropion was not associated with psychotomimetic effects, weight gain, or sexual dysfunction. CONCLUSIONS: In patients with major depression, dextromethorphan-bupropion (AXS-05) significantly improved depressive symptoms compared with bupropion and was generally well tolerated.


Asunto(s)
Bupropión , Trastorno Depresivo Mayor , Dextrometorfano , Adolescente , Adulto , Anciano , Bupropión/efectos adversos , Trastorno Depresivo Mayor/tratamiento farmacológico , Dextrometorfano/efectos adversos , Método Doble Ciego , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven
8.
J Occup Environ Med ; 64(5): 382-384, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35166255

RESUMEN

OBJECTIVE: Our aim was to describe the effectiveness of employee temperature screening at a public hospital in San Francisco during the COVID-19 pandemic. METHODS: An estimated 6000 health care personnel (HCP) underwent daily screening before entry to campus. Logs of failed employee entrance temperature screenings from March 2020 through March 2021 were reviewed. RESULTS: From March 2020 through March 2021, only one employee, who reported no symptom that could bar their entry to work, had an elevated temperature on screening. On re-check with an oral thermometer, that individual's temperature was normal. CONCLUSIONS: While the rationale to continue temperature screening may be rooted in beliefs it will increase employee reporting of symptoms or exposures, our results indicates that such screening of HCP at large US hospitals has no utility in detecting COVID-19 or controlling its transmission.


Asunto(s)
COVID-19 , COVID-19/epidemiología , Atención a la Salud , Personal de Salud , Humanos , Pandemias/prevención & control , SARS-CoV-2 , Temperatura
9.
Clin Infect Dis ; 74(4): 591-596, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34086881

RESUMEN

BACKGROUND: mRNA SARS-CoV-2 vaccines are administered to 2 million individuals per day in the United States under US Food and Drug Administration emergency use authorization. METHODS: Observational cohort study of hospital employees who received their first SARS-CoV-2 mRNA vaccination between 14 December 2020 and 8 January 2021, including employees who reported onset of an injection site reaction ≥48 hours after administration of their first or second dose to an employee hotline. RESULTS: Thirteen female employees who received the mRNA-1273 vaccine (Moderna) during the first 3 weeks of the SARS-CoV-2 vaccine rollout at San Francisco General Hospital reported a pruritic rash at the injection site appearing 3 -9 days after receipt of their initial dose. Five had milder or similar reactions with earlier onset after the second dose. One additional female employee reported this delayed reaction only after the second dose. None reported serious adverse events or had symptoms severe enough to seek medical attention. These cases represented 1.1% of the 1275 female employees who received their first mRNA-1273 dose and 2.0% of the 557 who were aged 31 -45 years during this initial vaccine rollout. None of 675 males who initiated mRNA-1273 or 3612 employees of any sex who initiated BNT162b (Pfizer) vaccination during this period reported delayed-onset reactions. CONCLUSIONS: These results suggest that delayed-onset, injection site pruritic rashes after mRNA-1273 SARS-CoV-2 vaccine administration, lasting up to 1 week, occur commonly in females, do not lead to serious sequela, and should not deter receipt of the second vaccine dose.


Asunto(s)
Vacuna nCoV-2019 mRNA-1273 , COVID-19 , Reacción en el Punto de Inyección/epidemiología , Vacuna nCoV-2019 mRNA-1273/efectos adversos , Adulto , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Estudios de Cohortes , Femenino , Hospitales , Humanos , Incidencia , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Estados Unidos/epidemiología
11.
Hepatol Commun ; 6(5): 1172-1185, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34783177

RESUMEN

Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with 68 Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored. In a subset (n = 30), messenger RNA (mRNA) data from the Cancer Genome Atlas HCC RNA sequencing were correlated with PSMA expression. In phase 2, 68 Ga-PSMA-11 PET was prospectively performed in patients with treatment-naïve HCC on a digital PET scanner using cyclotron-produced 68 Ga. Uptake was graded qualitatively and semi-quantitatively using standard metrics. On IHC, PSMA expression was significantly higher in HCC compared with CCA and HCA (P < 0.0001); 91% of HCCs (n = 134) expressed PSMA, which principally localized to tumor-associated neovasculature. Higher tumor grade was associated with PSMA expression (P = 0.012) but there was no association with tumor size (P = 0.14), fibrosis (P = 0.35), cirrhosis (P = 0.74), hepatitis B virus (P = 0.31), or hepatitis C virus (P = 0.15). Overall survival tended to be longer in patients without versus with PSMA expression (median overall survival: 4.2 vs. 1.9 years; P = 0.273). FGF14 (fibroblast growth factor 14) mRNA expression correlated positively (rho = 0.70; P = 1.70 × 10-5 ) and MAD1L1 (Mitotic spindle assembly checkpoint protein MAD1) correlated negatively with PSMA expression (rho = -0.753; P = 1.58 × 10-6 ). Of the 190 patients who met the eligibility criteria, 31 patients with 39 HCC lesions completed PET; 64% (n = 25) lesions had pronounced 68 Ga-PSMA-11 standardized uptake value: SUVmax (median [range] 9.2 [4.9-28.4]), SUVmean 4.7 (2.4-12.7), and tumor-to-liver background ratio 2 (1.1-11). Conclusion: Ex vivo expression of PSMA in neovasculature of HCC translates to marked tumor avidity on 68 Ga-PSMA-11 PET, which suggests that PSMA has the potential as a theranostic target in patients with HCC.


Asunto(s)
Neoplasias de los Conductos Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias de la Próstata , Conductos Biliares Intrahepáticos/metabolismo , Carcinoma Hepatocelular/diagnóstico por imagen , Ciclotrones , Radioisótopos de Galio , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/diagnóstico por imagen , Masculino , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones , Neoplasias de la Próstata/metabolismo , ARN Mensajero , Nanomedicina Teranóstica
13.
Am J Trop Med Hyg ; 104(6): 2169-2175, 2021 04 22.
Artículo en Inglés | MEDLINE | ID: mdl-33886500

RESUMEN

As coronavirus disease 2019 (COVID-19) spreads across Africa, little is known about the impact of the pandemic on health-care workers (HCWs) in the region. We designed an anonymous survey distributed via e-mail and phone messaging to 13 countries through the African Hepatitis B Network. We obtained 489 analyzable responses. We used risk ratio analysis to quantify the relationship between binary variables and χ2 testing to quantify the statistical significance of these relationships. Median age of respondents was 30 years (interquartile range, 26-36 years) and 63% were physicians. The top three sources of information used by HCWs for COVID-19 management included the Ministry of Health of each country, the WHO, and social media. Forty-nine percent reported a decrease in income since the start of the pandemic, with the majority experiencing between a 1% and a 25% salary reduction. Sixty-six percent reported some access to personal protective equipment; only 14% reported appropriate access. Moreover, one third of respondents reported no availability of ventilators at their facility. Strikingly, the percentage of HCWs reporting never feeling depressed changed from 61% before the pandemic to 31% during the pandemic, with a corresponding increase in daily depressive symptoms from 2% to 20%. Most respondents (> 97%) correctly answered survey questions about COVID-19 symptoms, virus transmission, and prevention. Our survey revealed African HCWs face a variety of personal and professional context-dependent challenges. Ongoing support of HCWs through and after the COVID-19 pandemic is essential.


Asunto(s)
COVID-19/epidemiología , COVID-19/psicología , Personal de Salud/economía , Personal de Salud/psicología , SARS-CoV-2 , Adulto , África/epidemiología , COVID-19/economía , Recolección de Datos , Femenino , Humanos , Masculino , Equipo de Protección Personal
15.
Appl Radiat Isot ; 168: 109560, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33321370

RESUMEN

A single HPIC method was developed and validated for the analysis of both [11C]Choline and [13N]Ammonia with the same setup. The HPIC system suitability tests were performed and [11C]Choline and [13N]Ammonia were used to verify their performance on this HPIC method. The HPIC setup and method provides qualitative and quantitative analysis information of [11C]Choline and [13N]Ammonia. The data suggested this HPIC method is validated for determining radiochemical/chemical purity and radiochemical identity of [11C]Choline and [13N]Ammonia products in CGMP compliant manufacturing process.

16.
Semin Nucl Med ; 50(6): 549-561, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33059824

RESUMEN

Perfusion, as measured by imaging, is considered a standard of care biomarker for the evaluation of many tumors. Measurements of tumor perfusion may be used in a number of ways, including improving the visual detection of lesions, differentiating malignant from benign findings, assessing aggressiveness of tumors, identifying ischemia and by extension hypoxia within tumors, and assessing treatment response. While most clinical perfusion imaging is currently performed with CT or MR, a number of methods for PET imaging of tumor perfusion have been described. The inert PET radiotracer 15O-water PET represents the recognized gold standard for absolute quantification of tissue perfusion in both normal tissue and a variety of pathological conditions including cancer. Other cancer PET perfusion imaging strategies include the use of radiotracers with high first-pass uptake, analogous to those used in cardiac perfusion PET. This strategy produces more visually pleasing high-contrast images that provide relative rather than absolute perfusion quantification. Lastly, multiple timepoint imaging of PET tracers such as 18F-FDG, are not specifically optimized for perfusion, but have advantages related to availability, convenience, and reimbursement. Multiple obstacles have thus far blocked the routine use of PET imaging for tumor perfusion, including tracer production and distribution, image processing, patient body coverage, clinical validation, regulatory approval and reimbursement, and finally feasible clinical workflows. Fortunately, these obstacles are being overcome, especially within larger imaging centers, opening the door for PET imaging of tumor perfusion to become standard clinical practice. In the foreseeable future, it is possible that whole-body PET perfusion imaging with 15O-water will be able to be performed in a single imaging session concurrent with standard PET imaging techniques such as 18F-FDG-PET. This approach could establish an efficient clinical workflow. The resultant ability to measure absolute tumor blood flow in combination with glycolysis will provide important complementary information to inform prognosis and clinical decisions.


Asunto(s)
Neoplasias/diagnóstico por imagen , Neoplasias/fisiopatología , Imagen de Perfusión , Tomografía de Emisión de Positrones , Humanos
17.
J Nucl Med Technol ; 48(3): 263-268, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32277061

RESUMEN

Acceptable and reproducible radiochemical purity (RP) for 68Ga-DOTATATE was difficult to obtain with the NETSPOT kit because the manufacturer instructions lacked details on the heater or needles used. Methods: The drug was prepared in an International Organization for Standardization (ISO) 5 environment. Multiple dry baths and needle types were used to investigate the effects of reaction temperature and metal contamination, respectively. Temperature curves were obtained with a calibrated thermocouple. The influence of the accuracy of the NETSPOT reagent volume and its effect on outcome were investigated. Results: The AccuBlock dry bath required recalibration for the ISO 5 environment; after calibration, the temperature was stable (only ±0.1°C from the set point). When we followed package insert recommendations (dry bath temperature set to 98°C, reaction time of 8 min), the reaction temperature was 90.6°C. When Becton Dickinson needles were used for reconstitution, 15 of 18 runs (83%) did not meet the RP specification. However, B. Braun Medical needles achieved satisfactory and stable RP. When the 68Ga generator was eluted with 5.0 mL of 0.1 M hydrochloric acid (HCl), only 3.8-3.9 mL of eluate reached the reaction vial; this volume did not impact labeling (final pH was 3.8). The labeling success rate increased markedly if the 68Ga eluate was passed through a conditioned silica gel cartridge or if no cartridge was used; then, RP was more than 99%. HCl contact with the septum of the labeling vial reduced RP. Conclusion: The needle type and the temperature setting of the dry bath have critical roles in 68Ga-DOTATATE preparation. The AccuBlock dry bath has excellent stability and accuracy and can be used for reliable preparation. By using a conditioned silica gel cartridge or by eliminating the cartridge altogether, the RP is reliably high and stable.


Asunto(s)
Compuestos Organometálicos/química , Radioquímica/métodos , Calibración , Concentración de Iones de Hidrógeno , Radioquímica/instrumentación , Temperatura
18.
Nucl Med Biol ; 80-81: 13-23, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31759313

RESUMEN

OBJECTIVE: The objectives of the present work were to optimize and validate the synthesis and stability of 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA) and 16-[18F]fluoro-4-thia-palmitic acid ([18F]FTP) under cGMP conditions for clinical applications. METHODS: Benzyl-14-(R,S)-tosyloxy-6-thiaheptadecanoate and methyl 16-bromo-4-thia-palmitate were used as precursors for the synthesis of [18F]FTHA and [18F]FTP, respectively. For comparison, a fatty acid analog lacking a thia-substitution, 16-[18F]fluoro-palmitic acid ([18F]FP), was synthesized from the precursor methyl 16-bromo-palmitate. A standard nucleophilic reaction using cryptand (Kryptofix/K222, 8.1 mg), potassium carbonate (K2CO3, 4.0 mg) and 18F-fluoride were employed for the 18F-labeling and potassium hydroxide (0.8 M) was used for the post-labeling ester hydrolysis. The final products were purified via reverse phase semi-preparative HPLC and concentrated via trap and release on a C-18 plus solid phase extraction cartridge. The radiochemical purities of the [18F]fluorothia fatty acids and [18F]FP were examined over a period of 4 h post-synthesis using an analytical HPLC. All the syntheses were optimized in an automated TRACERlab FX-N Pro synthesizer. Liquid chromatography mass spectrometry (LCMS) and high resolution mass spectrometry (HRMS) was employed to study the identity and nature of side products formed during radiosynthesis and as a consequence of post-synthesis radiation induced oxidation. RESULTS: Radiosyntheses of [18F]FTHA, [18F]FTP and [18F]FP were achieved in moderate (8-20% uncorrected) yields. However, it was observed that the HPLC-purified [18F]fluorothia fatty acids, [18F]FTHA and [18F]FTP at higher radioactivity concentrations (>1.11 GBq/mL, 30 mCi/mL) underwent formation of 18F-labeled side products over time but [18F]FP (lacking a sulfur heteroatom) remained stable up to 4 h post-synthesis. Various radiation protectors like ethanol and ascorbic acid were examined to minimize the formation of side products formed during [18F]FTHA and [18F]FTP synthesis but showed only limited to no effect. Analysis of the side products by LCMS showed formation of sulfoxides of both [18F]FTHA and [18F]FTP. The identity of the sulfoxide side product was further confirmed by synthesizing a non-radioactive reference standard of the sulfoxide analog of FTP and matching retention times on HPLC and molecular ion peaks on LC/HRMS. Radiation-induced oxidation of the sulfur heteroatom was mitigated by dilution of product with isotonic saline to reduce the radioactivity concentration to <0.518 GBq/mL (14 mCi/mL). CONCLUSIONS: Successful automated synthesis of [18F]fluorothia fatty acids were carried out in cGMP facility for their routine production and clinical applications. Instability of [18F]fluorothia fatty acids were observed at radioactivity concentrations exceeding 1.11 GBq/mL (30 mCi/mL) but mitigated through dilution of the product to <0.518 GBq/mL (14 mCi/mL). The identities of the side products formed were established as the sulfoxides of the respective thia fatty acids caused by radiation-induced oxidation of the sulfur heteroatom.


Asunto(s)
Ácidos Grasos/química , Radioisótopos de Flúor/química , Radioquímica/métodos , Oxidación-Reducción
20.
Am J Dermatopathol ; 42(2): 129-132, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31464721

RESUMEN

We present 2 patients with chronic discoid lupus erythematosus (LE) associated with xanthomatized macrophages on light microscopic findings. Skin biopsies revealed hyperkeratotic and atrophic epidermis, vacuolar degeneration of the dermal-epidermal junction, thickened basement membrane, follicular plugging, and perivascular and perifollicular lymphohistiocytic infiltrate. Notably, large collections of lipid-laden histiocytes were observed within the subjacent dermis. The patients denied history of intralesional steroid treatment. The patients did not demonstrate any clinical or laboratory signs of hyperlipidemia, cholestasis, and diabetes mellitus and insipidus. Accumulation of lipid-laden foam cells in cutaneous LE is a rare phenomenon that has been reported in discoid LE and lupus panniculitis, each only once in the literature. It has also been described within lesions of various other dermatoses in patients without lipid, hepatic, or endocrine abnormalities. Its mechanism remains unclear, but it has been hypothesized that intracellular lipids released from degenerating cells contribute to lipidization of mononuclear scavengers. Xanthomatous infiltration in cutaneous LE is an unusual feature, and its presence may not necessarily signify an underlying metabolic disorder.


Asunto(s)
Lupus Eritematoso Discoide/patología , Macrófagos/patología , Adulto , Femenino , Humanos , Masculino
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