CXCR4-DIRECTED [68GA]GA-PENTIXAFOR PET/CT AS A NOVEL DIAGNOSTIC MODALITY IN PRIMARY ALDOSTERONISM

Abstract

Objective: Primary aldosteronism (PA) is caused by autonomous production of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction (‘subtyping’) is crucial, PA is cured by adrenalectomy in unilateral PA and is treated by medication in bilateral PA. Subtyping is currently done by adrenal vein sampling (AVS). We propose a new diagnostic imaging modality employing the PET-tracer [68Ga] Ga-PentixaFor. This tracer reportedly has high uptake in APAs, whereas uptake is low in BAH or normal adrenals. The goal of this study is to determine concordance of [68Ga] Ga-PentixaFor PET/CT and AVS. Secondary outcomes are optimal timepoint for scanning and quantitative criteria for lateralization at the optimal timepoint. Design and method: This study is step 1 of a two-step randomized controlled diagnostic trial. We included patients with PA from Radboudumc Nijmegen and UMC Utrecht, confirmed by an intravenous salt-loading test. Patients underwent AVS and [68Ga]Ga-PentixaFor PET/CT. A dynamic scan was performed to determine optimal timepoint for scanning in the first 6 patients. The main outcome was the concordance of AVS and [68Ga]Ga-PentixaFor PET/CT. The SUVmax was used to determine lateralization in [68Ga]Ga-PentixaFor PET/CT. Results: Nineteen patients underwent adrenal vein sampling and a [68Ga]Ga-PentixaFor PET/CT. The optimal timepoint of scanning was 1h post injection. AVS showed lateralization in 13/19 patients. Using a cut-off of SUV¬max-ratio of 1.4, concordance was 68%. (figure 1) Using a Bayesian prediction model, the predicted concordance is: 67% (CI80% = 53 - 79). Figure 1: Scatter dot plot of the SUVmax Ratio in patients who had lateralization or no lateralization on AVS with a cut-off value of 1.4. Conclusions: [68Ga]Ga-PentixaFor PET/CT is a new imaging modality with high concordance with AVS. It is safe, readily available and as an out-patient procedure has the potential to improve subtyping in PA. With these preliminary results we have sufficient evidence of concordance to proceed to step 2 of the two-step trial: A pragmatic randomized controlled diagnostic trial, in which patients will be randomized in either [68Ga]Ga-PentixaFor PET/CT or AVS.