Functional adrenal imaging with 11C-prucalopride in primary aldosteronism – FIPPA

Primary aldosteronism (PA) is the most frequent cause and possibly curable form of secondary arterial hypertension. PA is characterized by an aldosterone excess which is usually caused by either a unilateral adrenocortical aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). Bilateral adrenal venous sampling (AVS) is currently recommended to distinguish APA from BAH and subsequently guide therapeutic decision-making but the method is invasive, not standardized and not widely available. Our team (INSERM U1239, University of Rouen Normandie) has previously shown that APAs overexpress the serotonin receptor type 4 (5-HT4R). The aim of the present translational “proof-of-concept” research project is to evaluate the feasibility and diagnostic accuracy of a new adrenal imaging technique using the radiolabelled 5-HT4R ligand 11C-prucalopride as an alternative to AVS. All patients enrolled in the study will undergo PET-scan 11C-prucalopride imaging in addition to the usual investigations recommended for the diagnostic course of PA. In addition, adrenal tissues removed from patients with APA will be processed for in vitro studies aimed at evaluating expression and functionality of the 5-HT4R using diverse approaches. The main objective of the project will be to assess the sensitivity and specificity of PET-scan 11C-prucalopride imaging for establishing the source of aldosterone excess using AVS as a gold standard. Secondary objectives will include the search for correlation between the adrenal uptake of the tracer in vivo and the expression data of the 5-HT4R obtained in vitro. The partners involved in the research consortium will combine expert hospital practitioners in the field of PA management and nuclear medicine, chemists specialized in synthesis of radiolabeled 5-HT4R ligands and skilled biologists for the characterization of 5HT4R in adrenal tissues, ensuring thus the feasibility of the experimental project.