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

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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.