Evaluation of [68Ga]Ga-PentixaFor PET Imaging for Detecting Unilateral Adrenal Aldosterone Secretion in Primary Aldosteronism Patients

The primary objective of this study is to evaluate whether **[68Ga]Ga-PTF-PET imaging** can effectively discriminate between patients with lateralized and non-lateralized secretion of aldosterone in adrenal glands, as classified by adrenal venous sampling (AVS). This is clinically relevant for the management of patients with **primary aldosteronism**, as it may guide therapeutic decisions regarding surgical intervention or medical management.

Secondary objectives include:

• Studying the correlation between the ratio of SUVmax on **[68Ga]Ga-PTF-PET imaging** between the hypersecreting adrenal gland and the contralateral adrenal gland, and the lateralization index during AVS.
• Measuring the correlation between the ratio of SUVmax on **[68Ga]Ga-PTF-PET imaging** between both adrenal glands and the mean SUVmax of the liver.
• Investigating the association between the ratio of SUVmax on **[68Ga]Ga-PTF-PET imaging** and the evolution of aldosterone secretion post-surgical adrenalectomy.
• Exploring the association between SUVmax on **[68Ga]Ga-PTF-PET imaging** in the hypersecreting adrenal gland and CXCR4 expression by immunohistochemistry.
• Assessing the correlation between SUVmax and SUVmean on **[68Ga]Ga-PTF-PET imaging** in the hypersecreting adrenal gland and the adenoma size on CT and histology.
• Analyzing the safety and tolerance of **[68Ga]Ga-PentixaFor** injections.
• Examining the association between SUVmax on **[68Ga]Ga-PTF-PET imaging** in the hypersecreting adrenal gland and CYP11B2 expression by immunohistochemistry.
• Studying the correlation between the primary endpoints and the mutation status of the adenomas.

The clinical trial involves participants diagnosed with **primary aldosteronism**, a condition characterized by excessive production of aldosterone. The study population includes both male and female subjects aged 18 years and older. Participants are required to have a confirmed diagnosis of primary aldosteronism, with or without adrenal nodules, and must have undergone adrenal venous sampling (AVS) to confirm unilateral or bilateral aldosterone secretion. The trial does not include a vulnerable population. Participants must be affiliated with French Social Security, and women of childbearing age are required to use effective contraception. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the efficacy of **[68Ga]Ga-PentixaFor** PET imaging in identifying unilateral adrenal secretion of aldosterone in patients diagnosed with **primary aldosteronism**. This study is structured as a randomized, double-blind, controlled trial, with an estimated duration from September 2024 to September 2027. Participants will be involved in the study for a period that includes initial screening, imaging procedures, and follow-up assessments. The trial will commence with a screening visit to confirm eligibility based on criteria such as age, informed consent, and diagnosis of primary aldosteronism, with or without adrenal nodules, confirmed by adrenal venous sampling (AVS).

Following the screening, participants will undergo the investigational procedure involving the intravenous administration of **[68Ga]Ga-PentixaFor**, a **solution for injection**. The primary endpoint is to measure the **SUVmax** (Standardized Uptake Value maximum) between both adrenal glands using PET imaging, with secondary endpoints including the aldosterone-to-cortisol ratio and lateralization index during AVS. Follow-up visits will be scheduled to monitor the safety and tolerance of the injection, assess any adverse events, and evaluate the persistence of primary aldosteronism post-surgical adrenalectomy. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any remaining health assessments are completed.

Participants are expected to remain in the study unless conditions arise that necessitate early termination, such as significant adverse events or withdrawal of consent. The trial aims to provide insights into the potential of **[68Ga]Ga-PentixaFor** PET imaging as a diagnostic tool for differentiating lateralized from non-lateralized aldosterone secretion, thereby aiding in the management of primary aldosteronism. The study will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the findings.

The clinical trial involves the use of the experimental medication **[68Ga]Ga-PentixaFor**, which is a **solution for injection**. This investigational product is designed for intravenous administration. The active substances in this formulation are **gallium (68Ga)** and **pentixafor**, both of which are of chemical origin. The maximum daily dose and total dose for the treatment period is 200 MBq (megabecquerels), with the treatment period limited to a single day. The primary objective of the trial is to evaluate the efficacy of **[68Ga]Ga-PentixaFor** PET imaging in identifying unilateral adrenal secretion of aldosterone in patients diagnosed with primary aldosteronism. The product is manufactured by PentixaPharm AG and is classified under the ATC code V09IX, which pertains to other diagnostic radiopharmaceuticals for tumor detection.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified for use in this study. The administration of the investigational product is monitored to ensure compliance with the dosing schedule, and participants are required to adhere strictly to the intravenous route of administration. The trial does not involve any pediatric formulations, and the investigational product is not classified as an orphan drug. The study is designed to assess the potential of **[68Ga]Ga-PentixaFor** in providing diagnostic insights into the lateralization of aldosterone secretion, which is critical for the management of primary aldosteronism.

Efficacy in the clinical trial will be assessed using several primary and secondary endpoints. The primary endpoints focus on the evaluation of **SUVmax** (Standardized Uptake Value maximum) in both adrenal glands using [68Ga]Ga-PentixaFor PET imaging. This includes measuring the higher SUVmax between the adrenal glands, calculating the ratio of SUVmax between the glands, determining the difference in SUVmax, and comparing the higher SUVmax with the mean SUV of the liver.

Secondary endpoints include a variety of assessments: the aldosterone-to-cortisol ratio between the two adrenal veins during adrenal venous sampling (AVS), the lateralization index during AVS, and the ratio of the highest SUVmax among the adrenal glands to the mean SUV of the liver. Additionally, the secretion of aldosterone will be assessed through blood tests post-surgical adrenalectomy, with results dichotomized into persistence of primary aldosteronism at six months. Other secondary endpoints involve evaluating CXCR4 expression levels via immunohistochemistry, adenoma sizes on CT and histology, safety and tolerance of [68Ga]Ga-PentixaFor injections, serious adverse events, CYP11B2 expression levels, and the somatic mutation status of hypersecreting adrenal glands and aldosterone-producing adenomas (APA).