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

原发性醛固酮增多症（PHA）是一种重要的、可治疗的高血压（高血压）形式，由肾上腺醛固酮激素分泌过多引起。醛固酮作用于肾脏保留钠（“盐”）；过量的钠潴留会导致高血压，增加中风、心脏病发作和肾衰竭的风险。PHA约占高血压患者的10%，占病情难以控制患者的20-25%。PHA几乎总是由于一个肾上腺的单一良性肿瘤（腺瘤），或两个腺体的弥漫性“过度生长”（双侧增生，BAH）。区分这些是至关重要的：手术切除腺瘤通常可以治愈PHA；BAH需要终生服药治疗。然而，目前用于肾上腺辅助诊断的标准检查，计算机断层扫描和磁共振扫描，都不敏感。而另一种主要技术肾上腺静脉取样（AVS），即从排出肾上腺的静脉中采血来测量醛固酮水平，对患者来说是高度侵入性的，耗时，困难，并且在20-50%的病例中失败。因此，需要一种更准确的、侵入性更小的PHA诊断方法。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，并使用一种基于化学美咪酯的化合物，这种化合物与制造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是一种诊断PHA的有力手段，目前正在进行一项主要的临床试验，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可以制备放射性药物的中心使用，因为放射性药物衰变很快，所以必须在1小时内使用。因此，为了使这种成像方法在整个英国国民医疗服务体系中得到更广泛的应用，我们的目标是开发一种新版本的放射性药物，这种药物在更长的时间内稳定，因此可以在制造后使用5-6小时。这将使它能够在一个地点准备，然后运送到一个地区的几家医院，这些医院的成像扫描仪最远可达100-150英里。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的放射性药物，包括评估PHA患者。

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.