Development of a fluorine-18 radiopharmaceutical to enhance and establish adrenal imaging by positron emission tomography

开发氟 18 放射性药物以通过正电子发射断层扫描增强和建立肾上腺成像

基本信息

批准号：
MR/P01710X/1
负责人：
Franklin Aigbirhio
金额：
$ 156.02万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FP01710X%2F1
关键词：
Development fluorine 18 radiopharmaceutical enhance

项目摘要

Primary hyperaldosteronism (PHA) is an important, treatable form of hypertension (high blood pressure), caused by overproduction of the hormone aldosterone from the adrenal glands.Aldosterone acts on the kidney to retain sodium ('salt'); excessive sodium retention leads to hypertension with an increased risk of stroke, heart attack and kidney failure. PHA accounts for about 10% of patients with hypertension and 20-25% of patients whose condition is difficult to control. PHA is almost always due to a single, benign tumour (adenoma) of one adrenal gland, or diffuse 'overgrowth' of both glands (bilateral hyperplasia, BAH). Distinguishing between these is critical: surgical removal of an adenoma often cures the PHA; BAH is treated with lifelong medication.However, at present standard investigations into the adrenal to help diagnosis, computed tomography and magnetic resonance scanning, are not sensitivity. While the other main technique adrenal vein sampling (AVS) which involves taking blood from the veins that drain both adrenal glands to measure aldosterone levels is highly invasive for patients, time-consuming, difficult to do and fails in 20-50% of cases. Therefore, there is a need for a more accurate method for diagnosing PHA, that is also less invasive.To address this need, our solution is to use the imaging technique of positron emission tomography (PET) coupled with using a compound based on the chemical metomidate, which binds to the protein which makes aldosterone. Radioactively 'tagged' to make a radiopharmaceutical this then provide a powerful mean of imaging and assessing the adrenal gland. We have now showed this can be a powerful means to diagnosis PHA and are presently undertaking a major clinical trial to compare it with AVS.However, at present this PET imaging technique can only be used at very few centres in the UK where the radiopharmaceutical can be prepared since it decays rapidly so must be used with 1 hr. Therefore, to enable wider access to this imaging method throughout the UK NHS our aim is to develop a new version of this radiopharmaceutical which is stable for a longer duration so can be used up to 5-6 hr after it has been manufactured. This will enable it to be prepared at one site and transported to several hospitals in a region with imaging scanners up to 100-150 mile away. Our aim in collaboration between researchers at Cambridge and Uppsala University Sweden is to develop this new radiopharmaceutical including assessing it patients with PHA.

原发性醛固酮增多症 (PHA) 是一种重要的、可治疗的高血压，由肾上腺产生过多的醛固酮激素引起。醛固酮作用于肾脏以保留钠（“盐”）；过多的钠潴留会导致高血压，并增加中风、心脏病和肾衰竭的风险。 PHA约占高血压患者的10%和病情难以控制的患者的20-25%。 PHA 几乎总是由一个肾上腺的单个良性肿瘤（腺瘤）或两个腺体的弥漫性“过度生长”（双侧增生，BAH）引起。区分这些疾病至关重要：手术切除腺瘤通常可以治愈 PHA； BAH 需要终身药物治疗。然而，目前用于帮助诊断的肾上腺标准检查、计算机断层扫描和磁共振扫描并不敏感。而另一种主要技术肾上腺静脉采样 (AVS) 涉及从引流双侧肾上腺的静脉中抽取血液来测量醛固酮水平，这对患者来说具有高度侵入性，耗时且难以实施，并且在 20-50% 的病例中会失败。因此，需要一种更准确、侵入性更小的方法来诊断 PHA。为了满足这一需求，我们的解决方案是使用正电子发射断层扫描 (PET) 成像技术，并结合使用基于化学物质的化合物甲咪酯，与产生醛固酮的蛋白质结合。通过放射性“标记”来制造放射性药物，这为肾上腺成像和评估提供了一种强大的手段。我们现在已经证明，这可以成为诊断 PHA 的有力手段，并且目前正在进行一项重大临床试验，将其与 AVS 进行比较。然而，目前这种 PET 成像技术只能在英国极少数中心使用，这些中心可以使用放射性药物。请做好准备，因为它会迅速腐烂，因此必须在 1 小时内使用。因此，为了在整个英国 NHS 范围内更广泛地使用这种成像方法，我们的目标是开发这种放射性药物的新版本，该药物在较长时间内保持稳定，因此在制造后最多可使用 5-6 小时。这将使它能够在一个地点准备好并运送到一个地区的几家医院，该地区的成像扫描仪距离最远 100-150 英里。我们剑桥大学和瑞典乌普萨拉大学的研究人员合作的目标是开发这种新型放射性药物，包括对 PHA 患者进行评估。