Tom Kurzawinski

Tom Kurzawinski

Mr Kurzawinski is an Endocrine Surgeon in London.

Bio

Imaging Aldosterone Driven Hypertension – New Research Project at UCL/UCLH

Primary Hyperaldosteronism (PHA) also known as Conns Syndrome is a severe form of hypertension caused by the overproduction of the hormone aldosterone in the adrenal glands and affects 1 in 10 people with high blood pressure. If left untreated it often leads to life threatening conditions, such as heart attack, stroke, kidney disease and dementia.

Hypertension in patients with PHA is difficult to control and they need to take a number of medications (3-5 drugs) for the rest of their life. However, in about half of them removal of the single adrenal that produces too much aldosterone can cure the high blood pressure and reduce the need for medications lowering blood pressure. 

Current diagnostic pathways stratifying for curative adrenalectomy is cumbersome, time consuming and costly It is therefore not surprising that only 1 in 1000 patients with this condition is correctly identified and appropriately treated. It is estimated that in the UK alone there is at least half a million of patients with PHA but only fewer than 300 adrenalectomies for unilateral form of PHA are performed each year.

UCL Centre for Radiopharmaceutical Chemistry has developed a highly selective aldosterone synthase PET tracer which we called AldoView and which could be used as a diagnostic tool to better identify and stratify patients with PHA for surgery. The aim of our research is to validate AldoView in two interlinked projects, laboratory study based on working with human adrenal tissue samples (d’ART) and first in human AldoView PET scanning (IDEAL). This research is funded by DPFS Biomedical Catalyst MRC (MRC Reference: MR/S037349/1).

D’ART

Development of Novel Positron Emission Tomography Adrenal Radio-Tracer for Diagnosis and Image Guided Therapy in Patients with PHA” (d’ART) is a laboratory study in which we will correlate the amount of aldosterone synthase detected by autoradiography ([18F]UCB2) and immunohistochemistry (CYP11B2) in resected adrenal glands from patients with PHA, Cushing and Phaeochromocytoma and kidney donors. In particular, we will analyse how well the radiotracer performs to (i) distinguish diseased areas of the adrenals (with abnormally high levels of aldosterone synthase) from healthy areas, (ii) differentiate PHA from other diseases caused by lesions in the adrenal glands, and (iii) detect tiny, but potentially very aggressive lesions that are easily missed in the current diagnostic procedure. 

IDEAL

Image-Derived Enzymatic Adrenal Lateralisation of Primary Hyperaldosteronism” (IDEAL). is the “first-in-human” clinical study where 12 patients with PHA will have PET/CT with AldoView and adrenalectomy. The aim of this study is to gather pilot data regarding the in vivo quantification of aldosterone synthase (CYP11B2) expression confirmed by histopathological analysis. In order to achieve this, we first need to understand tracer binding in the adrenal glands, to determine the optimal time window for imaging, and understand the biodistribution and dosimetry of the tracer. For this we will image patients and take venous blood samples at various time points to create Time-activity curves. This feasibility study will allow us an estimate of the effect size and its standard deviation, which will help to inform a sample size calculation for a subsequent clinical trial.

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