acetazolamide

乙酰唑胺
  • 文章类型: English Abstract
    BACKGROUND: Idiopathic intracranial hypertension (IIH) or benign intracranial hypertension is a rare disease in childhood. The clinical presentation in pediatric patients can be very variable, being more unespecific in younger patients.
    METHODS: A retrospective descriptive study was carried out on patients diagnosed of IIH in the last eight years (2016-2023) in the neuropediatrics unit of a tertiary hospital. In the present study, the clinical-epidemiological characteristics and the diagnostic-therapeutic procedure carried out in each case were analyzed.
    RESULTS: We studied 14 patients, 57% were women. The average age at diagnosis was 9 years, headache was the most common reason for consultation. In all patients, papilledema was found in the fundus and neuroimaging didn´t find alterations. Optical coherence tomography has been carried out in 78.5% of the sample, > 80% of patients showed thickening of the retinal nerve fiber layer. All patients had a high cerebrospinal fluid opening pressure (>25 cmH2O). 57% of patients required treatment with acetazolamide, a carbonic anhydrase inhibito. In all patients the resolution was complete, however almost 30% of them have presented recurrences during follow-up.
    CONCLUSIONS: In recent years there has been an increase in the incidence of this entity, making early diagnosis and treatment essential to avoid possible irreversible damage.
    BACKGROUND: Hipertensión intracraneal idiopática. Revisión de nuestra experiencia en los últimos ocho años (2016-2023).
    Introducción. La hipertensión intracraneal idiopática (HII), o hipertensión intracraneal benigna, es una enfermedad poco frecuente en la infancia. La presentación clínica en pacientes pediátricos puede ser muy variable, y es más inespecífica a menor edad. Pacientes y métodos. Se ha realizado un estudio descriptivo retrospectivo de los pacientes diagnosticados de HII en los últimos ocho años (2016-2023) en la consulta de neuropediatría de un hospital de tercer nivel. En el presente estudio se analizaron las características clinicoepidemiológicas y el procedimiento diagnosticoterapéutico llevado a cabo en cada caso. Resultados. Se estudió a 14 pacientes, de los cuales el 57% eran mujeres. La edad media en el momento del diagnóstico fue de 9 años, y la cefalea fue el motivo de consulta más habitual. En todos los pacientes se constató papiledema en el fondo de ojo y una prueba de neuroimagen sin alteraciones. Se llevó a cabo una tomografía de coherencia óptica en el 78,5% de la muestra, y >80% de los pacientes presentaba engrosamiento de la capa de fibras nerviosas retiniana. La totalidad de los pacientes presentaba una presión de apertura de líquido cefalorraquídeo elevada (> 25 cmH2O). El 57% de los pacientes precisó como tratamiento acetazolamida, un inhibidor de la anhidrasa carbónica. En todos los pacientes la resolución fue completa; sin embargo, casi el 30% de ellos presentó recurrencias durante el seguimiento. Conclusiones. En los últimos años se ha mostrado un aumento en la incidencia de esta entidad, y es fundamental un diagnóstico y un tratamiento precoces para evitar posibles secuelas irreversibles.
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  • 文章类型: Systematic Review
    急性心力衰竭(AHF)通常由于液体超负荷而导致不利的结果。虽然利尿剂是治疗的基石,乙酰唑胺可以通过减少钠的重吸收来提高利尿效率。与利尿剂治疗相比,我们对乙酰唑胺作为AHF患者的附加治疗效果进行了系统评价和荟萃分析。PubMed,Embase,在Cochrane数据库中搜索随机对照试验(RCT).采用随机效应模型来计算平均差异和风险比。使用R软件进行统计学分析。等级方法用于对证据的确定性进行评级。我们纳入了4个RCTs,634例患者,年龄68至81岁。平均随访3天至34个月,乙酰唑胺在给药48小时后显着增加了利尿(MD899.2mL;95%CI249.5至1549;p<0.01)和利钠(MD72.44mmol/L;95%CI39.4至105.4;p<0.01)。乙酰唑胺的使用与WRF(RR2.4;95%CI0.4~14.2;p=0.3)或全因死亡率(RR1.2;95%CI0.8~1.9;p=0.3)无相关性。干预组的临床充血率明显高于干预组(RR1.35;95%CI1.09至1.68;p=0.01)。乙酰唑胺是AHF患者的有效附加疗法,增加利尿,利钠尿,和临床充血,但与死亡率差异无关.
    Acute heart failure (AHF) often leads to unfavorable outcomes due to fluid overload. While diuretics are the cornerstone treatment, acetazolamide may enhance diuretic efficiency by reducing sodium reabsorption. We performed a systematic review and meta-analysis on the effects of acetazolamide as an add-on therapy in patients with AHF compared to diuretic therapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCT). A random-effects model was employed to compute mean differences and risk ratios. Statistical analysis was performed using R software. The GRADE approach was used to rate the certainty of the evidence. We included 4 RCTs with 634 patients aged 68 to 81 years. Over a mean follow-up of 3 days to 34 months, acetazolamide significantly increased diuresis (MD 899.2 mL; 95% CI 249.5 to 1549; p < 0.01) and natriuresis (MD 72.44 mmol/L; 95% CI 39.4 to 105.4; p < 0.01) after 48 h of its administration. No association was found between acetazolamide use and WRF (RR 2.4; 95% CI 0.4 to 14.2; p = 0.3) or all-cause mortality (RR 1.2; 95% CI 0.8 to 1.9; p = 0.3). Clinical decongestion was significantly higher in the intervention group (RR 1.35; 95% CI 1.09 to 1.68; p = 0.01). Acetazolamide is an effective add-on therapy in patients with AHF, increasing diuresis, natriuresis, and clinical decongestion, but it was not associated with differences in mortality.
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  • 文章类型: Journal Article
    虽然口服乙酰唑胺是治疗成人和儿童PTCS的基石,先前的研究表明,乙酰唑胺用于其他疾病的儿童可能会影响生长。
    涉及单个三级医疗中心的回顾性图表审查。确定了34名患有明确或可能的PTCS的儿童。分析仅限于在乙酰唑胺治疗之前和期间可获得人体测量数据的个体(n=22)。
    一半的个体(n=11/22)显示BMIZ得分下降。63%(n=14/22)在使用乙酰唑胺治疗期间显示身高Z评分降低;在这14名具有完整数据的儿童中,有6名,图3显示在停止乙酰唑胺后高度Z-评分的至少部分恢复。
    乙酰唑胺可能与某些接受儿童PTCS治疗的儿童的生长抑制有关。在某些情况下,一旦停止乙酰唑胺,生长抑制似乎逆转。
    UNASSIGNED: While oral acetazolamide is a cornerstone of management of adult and pediatric PTCS, previous studies have suggested that acetazolamide used in children with other conditions may influence growth.
    UNASSIGNED: Retrospective chart review involving a single tertiary medical center. Thirty-four children with definite or probable PTCS were identified. Analysis was restricted to individuals from whom anthropometric data were available before and during acetazolamide treatment (n=22).
    UNASSIGNED: Half of individuals (n=11/22) showed a decline in BMI Z-scores. Sixty-three percent (n=14/22) showed a decrease in height Z-scores during treatment with acetazolamide; in 6 of these 14 children who had complete data, 3 showed at least a partial recovery of height Z-scores after discontinuation of acetazolamide.
    UNASSIGNED: Acetazolamide may be associated with growth suppression in some children treated for pediatric PTCS. In some cases, the growth suppression appears to reverse once the acetazolamide is stopped.
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  • 文章类型: Journal Article
    进行这项系统回顾是为了更好地理解无数的演讲,各种治疗选择,对治疗的反应,及其在高磷血症性肿瘤钙质沉着症(HTC)中的临床结果。根据严格的纳入标准选择全文。HTC的所有病例报告,其中测量了基线磷酸盐,提到了提供的治疗,纳入了现有的随访和治疗反应信息.188项符合条件的研究中,共有43项(N=63例)符合纳入标准。提取了所需数据列表,并对方法质量进行了分级。共有63个人(男性=33)从43个合格的案例研究中纳入。患者的中位年龄为18(IQR8-32)岁。最常见的部位是髋关节/臀区(34/63;53.9%),其次是肘部/前臂(26/63;41.2%),和肩膀(18/63;28.5%)。三名患者有结膜钙化沉积。平均(SD)磷酸盐为6.9(1.1)mg/dL。在主题中,36/63(57.1%)接受了某种形式的药物治疗的手术切除。两名患者仅接受手术切除(2.1%)。1例患者维持随访(1.6%),24/63(38.1%)患者接受医学治疗。中位随访时间(IQR)为3(1-9)年。在19/63(30.2%)受试者中报告了病变大小的消退或减少;20/63(31.7%)显示进展,24/63(38.1%)具有疾病稳定的特征,3例患者报告死亡(4.7%).我们首次报告了HTC的临床和治疗反应的详细描述。旨在降低血清磷酸盐的综合医疗措施似乎是治疗的基石,尽管临床反应可能有所不同。
    This systematic review was performed to understand better the myriad presentations, various therapeutic options, response to therapy, and its clinical outcomes in hyperphosphatemic tumoral calcinosis (HTC). Full texts were selected according to strict inclusion criteria. All case reports of HTC wherein baseline phosphate was measured, treatment offered was mentioned, and information on follow-up and response to therapy that were available were included. A total of 43 of 188 eligible studies (N = 63 patients) met the inclusion criteria. A list of desired data was extracted and graded for methodological quality. A total of 63 individuals (Males = 33) were included from the 43 eligible case studies. The median age of the patients was 18 (IQR 8-32) years. The most frequently involved sites were the hip/gluteal region (34/63; 53.9%) followed by the elbow/forearm (26/63; 41.2%), and the shoulder (18/63; 28.5%). Three patients had conjunctival calcific deposits. The mean (SD) phosphate was 6.9 (1.1) mg/dL. Among the subjects, 36/63 (57.1%) underwent surgical excision with some form of medical therapy. Two patients underwent only surgical excision (2.1%). One patient was maintained on follow-up (1.6%) and 24/63 (38.1%) patients were treated with medical measures. The median (IQR) follow-up duration was 3 (1-9) years. Regression or reduction in lesion size was reported in 19/63 (30.2%) subjects; 20/63 (31.7%) showed progression, 24/63 (38.1%) had features of stable disease, and mortality was reported in 3 patients (4.7%). We report for the first time a detailed description of the clinical and therapeutic response of HTC. A combination of medical measures aimed at lowering serum phosphate appears to be the cornerstone of treatment, although clinical responses may vary.
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  • 文章类型: Journal Article
    眼睛的复杂结构对有效输送药物提出了挑战,这可以通过使用纳米技术来规避。本研究旨在使用简单的一步制造方法制备乙酰唑胺-loadedleciplex(ACZ-LP),然后采用32全因子设计进行优化。ACZ-LP具有很高的包封效率(93.25±2.32%),记录的平均直径约为171.03±3.32,单分散尺寸分布和zeta电位为41.33±2.10mV。制备的制剂的体外释放和离体渗透研究表明,与普通的乙酰唑胺溶液相比,在1小时内开始突释,然后是持续释放模式。此外,离体角膜药物保留(27.05±1.20%)和使用不同浓度粘蛋白的体外粘膜粘附研究表明,强静电结合证实了制剂的粘膜粘附特性。此外,组织病理学研究确保了制剂无刺激性和无毒,而HET-CAM确保了制剂的基本耐受性.在兔模型上进行的体内药效学研究表明,与普通乙酰唑胺溶液相比,用ACZ-LP治疗导致眼内压显著和延长的降低。乙酰唑胺口服片,和Brinzox®。总之,ACZ-LP是一种有效且通用的药物递送方法,在控制青光眼方面显示出显著的潜力.
    The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to prepareacetazolamide-loadedleciplex (ACZ - LP) using a simple one-step fabrication approach followed byoptimization employing a 32 Full Factorial Design. The ACZ - LP demonstrated high entrapment efficiency (93.25 ± 2.32 %), average diameter was recorded around 171.03 ± 3.32 with monodisperse size distribution and zeta potential of 41.33 ± 2.10 mV. Invitro release and ex vivo permeation studies of prepared formulation demonstrated an initial burst release in 1 h followed by sustained release pattern as compared to plain acetazolamide solution. Moreover, an ex vivo corneal drug retention (27.05 ± 1.20 %) and in vitro mucoadhesive studies with different concentration of mucin indicated strong electrostatic bonding confirming the mucoadhesive characteristics of the formulation. Additionally, the histopathological studies ensured that the formulation was non-irritant and nontoxic while and HET-CAM ensured substantial tolerability of the formulation. The in vivo pharmacodynamic investigation carried out on a rabbit model demonstrated that treatment with ACZ - LP resulted in a significant and prolonged reduction in intraocular pressure as compared to plain acetazolamide solution, acetazolamide oral tablet, and Brinzox®. In summary, the ACZ - LP is anefficient and versatile drug delivery approach which demonstrates significant potential in controlling glaucoma.
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  • 文章类型: Journal Article
    目的:这项现实生活中的研究旨在评估乙酰唑胺(ACZ)的安全性,一种具有利尿作用的碳酸酐酶抑制剂。ACZ最近被证明可以改善因急性心力衰竭(HF)住院的患者的充血。然而,缺乏安全性方面的数据。方法:我们从2023年11月至2024年2月在12张病床的心脏科进行了一项单中心观察性前瞻性研究,记录不良事件(低血压,严重的代谢性酸中毒,严重的低钾血症和肾脏事件)在院内HF治疗期间。在研究期间,所有因急性HF住院的患者在IV呋塞米(n=28,48.3%)的基础上接受ACZ(每天500mg,持续3天)治疗(n=30,51.7%)。结果:接受ACZ治疗的患者比没有接受ACZ治疗的患者年轻(中位年龄78(范围67-86)与85(79-90)年,分别,p=0.01),并且患有慢性肾脏疾病的频率较低(估计的肾小球分数中位数(60(35-65)与38(26-63)mL/min,p=0.02)。关于HF治疗期间的不良事件,低血压的发生率没有差异(ACZ组的3例患者[10.7%]与四个[13.3%],p=0.8),肾脏事件(ACZ组4例[14.3%]与五[16.7%],p=1)和严重低钾血症(ACZ组的两个[7.1%]与三个[10%],p=1)。两组均未发生严重代谢性酸中毒。结论:尽管基线时的临床特征不同,接受ACZ的患者年龄更小,肾功能更好,与单独接受呋塞米的患者相比,耐受性没有显著差异.需要更多的观察数据来进一步评估ACZ-呋塞米组合在HF住院管理中的安全性。尤其是在老年人中,脆弱的人口。
    Objectives: This real-life study aimed to evaluate the safety of acetazolamide (ACZ), a carbonic anhydrase inhibitor with diuretic effects. ACZ has recently been proven to improve decongestion in the context of patients hospitalized for acute heart failure (HF). However, data in terms of safety are lacking. Methods: We conducted a monocentric observational prospective study from November 2023 to February 2024 in a 12-bed cardiology department, recording adverse events (hypotension, severe metabolic acidosis, severe hypokalemia and renal events) during in-hospital HF treatment. All patients hospitalized for acute HF during the study period treated with ACZ (500 mg IV daily for 3 days) on top of IV furosemide (n = 28, 48.3%) were compared with patients who have been treated with IV furosemide alone (n = 30, 51.7%). Results: The patients treated with ACZ were younger than those without (median age 78 (range 67-86) vs. 85 (79-90) years, respectively, p = 0.01) and had less frequent chronic kidney disease (median estimated glomerular fraction rate (60 (35-65) vs. 38 (26-63) mL/min, p = 0.02). As concerned adverse events during HF treatment, there were no differences in the occurrences of hypotension (three patients [10.7%] in the ACZ group vs. four [13.3%], p = 0.8), renal events (four patients [14.3%] in the ACZ group vs. five [16.7%], p = 1) and severe hypokalemia (two [7.1%] in the ACZ group vs. three [10%], p = 1). No severe metabolic acidosis occurred in either group. Conclusions: Although the clinical characteristics differed at baseline, with younger age and better renal function in patients receiving ACZ, the tolerance profile did not significantly differ from patients receiving furosemide alone. Additional observational data are needed to further assess the safety of ACZ-furosemide combination in the in-hospital management of HF, especially in older, frail populations.
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  • 文章类型: Case Reports
    牵牛花盘异常是一种罕见的先天性异常,影响视盘,通常与视网膜脱离有关。本报告介绍了一个10岁男孩的独特病例,该男孩患有牵牛花盘异常和浆液性视网膜脱离,口服乙酰唑胺治疗。值得注意的是,出现大疱性脱离的视网膜的一半在开始乙酰唑胺治疗后的几天内重新连接,导致视力完全恢复.停药后无复发。口服乙酰唑胺可被认为是与非孔源性牵牛花椎间盘异常相关的视网膜脱离的替代治疗选择。[眼科手术激光成像视网膜2024;55:XX-XX.].
    Morning glory disc anomaly is a rare congenital anomaly affecting the optic disc and is frequently associated with retinal detachment. This report presents a unique case of a 10-year-old boy with morning glory disc anomaly and serous retinal detachment, treated with oral acetazolamide. Remarkably, half of the retina exhibiting bullous detachment was reattached leading to full recovery of vision within a few days after starting acetazol-amide treatment. There was no recurrence after discontinuation of medication. Oral acetazolamide can be considered an alternative treatment option for retinal detachment associated with morning glory disc anomaly of non-rhegmatogenous origin. [Ophthalmic Surg Lasers Imaging Retina 2024;55:415-417.].
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  • 文章类型: Journal Article
    目的:由于证据有限,鼻脑脊液(CSF)泄漏的围手术期处理不是自愿的。这项研究的主要目的是确定国际专家围手术期治疗鼻内镜下脑脊液漏修复的关键因素。
    方法:一项60项调查问卷收集了耳鼻喉科外科医师和神经外科医师国际学会成员对鼻腔填塞的意见,术后指示,抗生素预防,和脑脊液容量耗尽。
    结果:调查有153名受访者(124名耳鼻喉科医师和29名神经外科医师)。85%(130/151)的受访者建议前颅底脑脊液漏延长的静息位置,主要在福勒的位置(72%(110/153))。85%(130/153)的受访者使用鼻塞;33.3%(51/153)的受访者使用鼻塞来稳定重建,和22.2%(34/153)防止出血。在44.4%的病例(68/153)中,通常在48小时后将其清除。在CSF泄漏复发的情况下,有47.1%(72/153)的受访者认为CSF耗尽,在颅内压升高的情况下,有34.6%(53/153)的受访者认为CSF耗尽。所有受访者都向患者提供了具体的术后指导,包括驾驶,跑步,游泳,潜水限制和飞行限制。在亚组分析中,耳鼻喉科外科医生比神经外科医生更经常推荐休息姿势(71%vs.37.9%;p=0.0008),开了更多的抗生素(82.3%vs.21.4%;p<0.0001)。
    结论:尽管CSF闭合后的术后管理仍然具有挑战性,但尚未成文,这项国际调查揭示了一些关于休息位置和术后活动限制的共识。必须进行前瞻性临床研究以评估其效率。
    OBJECTIVE: Peri-operative management of nasal cerebrospinal fluid (CSF) leaks is not consensual due to limited evidence. The main aim of this study was to identify key factors in peri-operative management of endoscopic endonasal CSF leak repair among international experts.
    METHODS: A 60-item survey questionnaire collected opinions of members of international learned societies of ENT surgeons and neurosurgeons on nasal packing, post-operative instructions, antibiotic prophylaxis, and CSF volume depletion.
    RESULTS: The survey had 153 respondents (124 otorhinolaryngologists and 29 neurosurgeons). A resting position was recommended by 85% (130/151) of respondents for extended CSF leak of the anterior skull base, mainly in Fowler\'s position (72% (110/153)). Nasal packing was used by 85% (130/153) of respondents; 33.3% (51/153) used it to stabilize the reconstruction, and 22.2% (34/153) to prevent bleeding. It was usually removed after 48 h in 44.4% of cases (68/153). CSF depletion was considered by 47.1% (72/153) of respondents in case of CSF leak recurrence and by 34.6% (53/153) in cases of increased intracranial pressure. All respondents gave specific postoperative instructions to patients including driving, running, swimming, diving restrictions and flighting restrictions. In subgroup analysis, ENT surgeons more often recommended a resting position than neurosurgeons (71% vs. 37.9% ; p = 0.0008) and prescribed more antibiotics (82.3% vs. 21.4% ; p < 0.0001).
    CONCLUSIONS: Although postoperative management after CSF closure remains challenging and not codified, this international survey revealed some points of consensus concerning resting position and restriction of post-operative activities. Prospective clinical studies must be undertaken to evaluate their efficiency.
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  • 文章类型: Journal Article
    淋病奈瑟菌是一种常见的性传播疾病,与许多抗生素的广泛耐药性有关。目前,只有广谱头孢菌素(头孢曲松和头孢克肟)和阿奇霉素仍可用于其治疗.
    经典抗生素药物靶标促旋酶/拓扑异构酶IV的新化学型提供了与这些酶有效结合的抑制剂,通过与氟喹诺酮类药物不同的抑制机制,因此不易发生突变。来自该细菌基因组的α-碳酸酐酶(NgCAα)也被验证为抗菌靶标。
    通过利用促旋酶/拓扑异构酶IV的不同亚基以及新的化学型,两种新抗生素进入II/III期临床试验,佐利福达星和吉波地星。它们具有新的抑制机制,与氟喹诺酮类药物相比,在酶的不同部分结合。还报道了对这些酶具有抑制活性的其他化学型。获得了属于各种类型的NgCAα抑制剂,几种磺胺类药物的MIC值在0.25-4µg/mL范围内,在这种感染的动物模型中具有显着的活性。因此,乙酰唑胺和类似的CA抑制剂可能被重新用作抗感染药。科学/专利文献已在PubMed上搜索,ScienceDirect,Espacenet,和专利大师,从2016年到2024年。
    UNASSIGNED: Neisseria gonorrhoeae is a common sexually transmitted disease connected with extensive drug resistance to many antibiotics. Presently, only expanded spectrum cephalosporins (ceftriaxone and cefixime) and azithromycin remain useful for its management.
    UNASSIGNED: New chemotypes for the classical antibiotic drug target gyrase/topoisomerase IV afforded inhibitors with potent binding to these enzymes, with an inhibition mechanism distinct from that of fluoroquinolones, and thus less prone to mutations. The α-carbonic anhydrase from the genome of this bacterium (NgCAα) was also validated as an antibacterial target.
    UNASSIGNED: By exploiting different subunits from the gyrase/topoisomerase IV as well as new chemotypes, two new antibiotics reached Phase II/III clinical trials, zoliflodacin and gepotidacin. They possess a novel inhibition mechanism, binding in distinct parts of the enzyme compared to the fluoroquinolones. Other chemotypes with inhibitory activity in these enzymes were also reported. NgCAα inhibitors belonging to a variety of classes were obtained, with several sulfonamides showing MIC values in the range of 0.25-4 µg/mL and significant activity in animal models of this infection. Acetazolamide and similar CA inhibitors might thus be repurposed as antiinfectives. The scientific/patent literature has been searched for on PubMed, ScienceDirect, Espacenet, and PatentGuru, from 2016 to 2024.
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  • 文章类型: Journal Article
    碳酸酐酶IX(CAIX),锌金属跨膜蛋白,在95%的透明细胞肾细胞癌(ccRCC)中高表达。核医学成像技术中针对CAIX设计的正电子发射断层扫描(PET)探头可以实现精确定位,是非侵入性的,并可用于实时监测病变中CAIX的表达。在这项研究中,我们构建了一种新型的乙酰唑胺双靶向小分子探针[68Ga]Ga-LF-4,它通过与特定的氨基酸序列结合来靶向CAIX。衰减校正后,反应15分钟后,放射性标记产率达到66.95±0.57%(n=5),放射化学纯度达到99%(n=5)。[68Ga]Ga-LF-4具有良好的体外和体内稳定性,以及对CAIX的体内安全性和高亲和力,Kd值为6.62nM。此外,[68Ga]Ga-LF-4可以在体内从血液中快速清除。生物分布研究显示,[68Ga]Ga-LF-4信号集中在心脏,肺,和给药后的肾脏,这与micro-PET/CT研究中观察到的相同。在ccRCC患者来源的异种移植物(PDX)模型中,给药后,信号在肿瘤中显著积累,其中它被保留长达4小时。在用LF-4竞争性阻断后,在肿瘤部位的摄取显著降低。探针[68Ga]Ga-LF-4在ccRCC肿瘤部位的SUVmax是PC3组的三倍,在30分钟时CAIX表达较低(ccRCCvsPC3:1.86±0.03vs0.62±0.01,t=48.2,P<0.0001)。这些结果表明[68Ga]Ga-LF-4是靶向CAIX的新型小分子探针,可用于对局部和转移性ccRCC病变成像。
    Carbonic anhydrase IX (CAIX), a zinc metal transmembrane protein, is highly expressed in 95% of clear cell renal cell carcinomas (ccRCCs). A positron emission tomography (PET) probe designed to target CAIX in nuclear medicine imaging technology can achieve precise positioning, is noninvasive, and can be used to monitor CAIX expression in lesions in real time. In this study, we constructed a novel acetazolamide dual-targeted small-molecule probe [68Ga]Ga-LF-4, which targets CAIX by binding to a specific amino acid sequence. After attenuation correction, the radiolabeling yield reached 66.95 ± 0.57% (n = 5) after 15 min of reaction and the radiochemical purity reached 99% (n = 5). [68Ga]Ga-LF-4 has good in vitro and in vivo stability, and in vivo safety and high affinity for CAIX, with a Kd value of 6.62 nM. Moreover, [68Ga]Ga-LF-4 could be quickly cleared from the blood in vivo. The biodistribution study revealed that the [68Ga]Ga-LF-4 signal was concentrated in the heart, lung, and kidney after administration, which was the same as that observed in the micro-PET/CT study. In a ccRCC patient-derived xenograft (PDX) model, the signal significantly accumulated in the tumor after administration, where it was retained for up to 4 h. After competitive blockade with LF-4, uptake at the tumor site was significantly reduced. The SUVmax of the probe [68Ga]Ga-LF-4 at the ccRCC tumor site was three times greater than that in the PC3 group with low CAIX expression at 30 min (ccRCC vs PC3:1.86 ± 0.03 vs 0.62 ± 0.01, t = 48.2, P < 0.0001). These results indicate that [68Ga]Ga-LF-4 is a novel small-molecule probe that targets CAIX and can be used to image localized and metastatic ccRCC lesions.
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