Gillett Daniel, Senanayake Russell, MacFarlane James, Bashari Waiel, Palma August, Hu Lihua, Harper Ines, Mendichovszky Iosif A, Antoni Gunnar, Hellman Per, Sundin Anders, Hird Matthew, Boros István, Brown Morris J, Cheow Heok, Aloj Luigi, Aigbirhio Franklin, Gurnell Mark
Cambridge Endocrine Molecular Imaging Group, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom.
Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge, United Kingdom.
J Nucl Med. 2025 Mar 3;66(3):434-440. doi: 10.2967/jnumed.124.268425.
Primary aldosteronism (PA) is a common, potentially reversible, cause of hypertension. Distinguishing unilateral from bilateral PA is critical when deciding who should be offered surgery (unilateral adrenalectomy). Recent studies have shown that PET/CT with [C]metomidate can accurately identify unilateral PA, with localization of the causative aldosterone-producing adenoma (APA). However, the availability of [C]metomidate is limited to centers with an on-site cyclotron. Here, we report an early-phase human study with the F-labeled analog, para-chloro-2-[F]fluoroethyletomidate ([F]CETO). We conducted a phase I/IIa, single-center, open-label, microdosing study. The primary objective was to evaluate the safety of up to 2 administrations of [F]CETO in 6 patients with PA (3 unilateral disease, 3 bilateral disease) and 5 healthy volunteers. Safety evaluation included assessment of adrenal function after the first [F]CETO administration. The biodistribution of [F]CETO was assessed in a 90-min dynamic PET acquisition. In patients with PA, the effect of pretreatment with oral dexamethasone on [F]CETO uptake by normal adrenal tissue and APAs was also assessed. Eleven participants were recruited to the trial, including 6 patients and 5 healthy volunteers. No subjects experienced serious adverse events or reactions, and all participants had normal adrenal function after [F]CETO administration. [F]CETO demonstrated high selectivity for the adrenal glands with low uptake in other tissues. Visualization of APAs was enhanced after dexamethasone pretreatment, which suppressed [F]CETO uptake by normal adrenal tissue. [F]CETO is a safe radiopharmaceutical for PET imaging of the adrenal glands, with no observed adverse reactions or impairment of adrenal function in this study. [F]CETO demonstrates selective high affinity for adrenal tissue, particularly APAs. Distinction between APAs and normal adrenal tissue is enhanced by dexamethasone pretreatment to suppress [F]CETO uptake by normal glands. This positions [F]CETO as a promising imaging tool for evaluation in the context of PA.
原发性醛固酮增多症（PA）是高血压常见的、潜在可逆转的病因。在决定谁适合接受手术（单侧肾上腺切除术）时，区分单侧PA和双侧PA至关重要。近期研究表明，使用[C]米托咪酯的PET/CT能够准确识别单侧PA，并定位产生醛固酮的腺瘤（APA）。然而，[C]米托咪酯仅在设有现场回旋加速器的中心才有。在此，我们报告一项关于F标记类似物对氯-2-[F]氟乙基米托咪酯（[F]CETO）的早期人体研究。我们开展了一项I/IIa期、单中心、开放标签的微剂量研究。主要目的是评估在6例PA患者（3例单侧病变、3例双侧病变）和5名健康志愿者中给予最多2次[F]CETO的安全性。安全性评估包括首次给予[F]CETO后对肾上腺功能的评估。在90分钟的动态PET采集过程中评估[F]CETO的生物分布。在PA患者中，还评估了口服地塞米松预处理对正常肾上腺组织和APA摄取[F]CETO的影响。11名参与者被纳入该试验，包括6例患者和5名健康志愿者。没有受试者经历严重不良事件或反应，且所有参与者在给予[F]CETO后肾上腺功能正常。[F]CETO对肾上腺表现出高选择性，在其他组织中的摄取较低。地塞米松预处理后APA的可视化增强，这抑制了正常肾上腺组织对[F]CETO的摄取。[F]CETO是一种用于肾上腺PET成像的安全放射性药物，在本研究中未观察到不良反应或肾上腺功能损害。[F]CETO对肾上腺组织，尤其是APA表现出选择性高亲和力。地塞米松预处理可抑制正常腺体对[F]CETO的摄取，从而增强APA与正常肾上腺组织之间的区分。这使[F]CETO成为PA背景下一种有前景的评估成像工具。
