Evaluation of [68Ga]Ga-PentixaFor PET Imaging for the Identification of Unilateral Adrenal Secretion of ALdosterON in Patients With Primary Aldosteronism

Phase 2

Not yet recruiting

Brief Summary: PentixaFor radiolabeled with 68Gallium (68Ga) is a radiopharmaceutical targeting the CXC chemokine receptor 4 (CXCR4) receptor. The CXCR4 receptor is expressed in zona glomerulosa of the adrenal cortex and in aldosterone producing adenoma (APA). The objective of this study will be to evaluate in 25 patients if \[68Ga\]Ga-PentixaFor positron emission tomography (\[68Ga\]Ga-PTF-PET) imaging allows for the discrimination of patients with lateralized or non-lateralized secretion of aldosterone in adrenal glands classified based on adrenal vein sampling (AVS).

Detailed Description: The identification of the cause of primary aldosteronism (PA) is critical because, in case of lateralized secretion of aldosterone, a surgical treatment can be offered to patients with the objective of full patient recovery, whereas in case of bilateral secretion, only a long-term medical treatment with mineralocorticoid receptor antagonists should be considered. The presence or absence of adrenal nodule on morphological imaging does not allow us to state on the lateralization or not of aldosterone secretion. Moreover, on one hand, the prevalence of adrenal incidentalomas, mostly non-secreting, can be detected in between 2 to 10% of general population. On the other hand, unilateral secretion of aldosterone exists in 30% of patients with normal adrenal glands on imaging. The AVS with measurements of the concentrations of aldosterone is the closest to a referral exam to confirm the diagnosis of lateralized secretion of aldosterone, but it is a complex and invasive procedure with only limited access to centers with expertise in invasive radiology and an important heterogeneity in interpretation. The development of noninvasive imaging approaches allowing for a more specific identification of lateralized vs. bilateral aldosterone secretion would, hence, have a major impact on the clinical management of these patients.

Recruitment & Eligibility

Inclusion Criteria

Age ≥ 18 years old
Signed written informed consent
French Social Security affiliation
For child-bearing aged women, effective form of contraception*
Diagnosis of primary aldosteronism:
With or without adrenal nodule on morphological imaging (CT or Magnetic Resonance Imaging)
With unilateral or bilateral aldosterone secretion confirmed by invasive AVS
- Such methods include: combined hormonal contraception, progestogen-only hormonal contraception, intrauterine device (IUD) or hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, condom, sexual abstinence.

Exclusion Criteria

Pregnant or breastfeeding women
Patient under legal protection (guardianship)
Contraindication to the PET-CT
Contraindication to the injection of [68Ga]Ga-PentixaFor
Participation in another interventional study involving human participants or being in the exclusion period at the end of a previous study involving human participants, if applicable
Patient on AME (state medical aid) (unless exemption from affiliation)
Completed group: if the expected number of patients has been reached (15 patients) in the corresponding group of patients (with lateralized or non-lateralized PA).

Arm && Interventions

Group	Intervention	Description
[68Ga]Ga-PentixaFor; single injection	[68Ga]Ga-PentixaFor PET imaging	\[68Ga\]Ga-PentixaFor; 150 (± 50) MBq intravenous injection over 30 seconds; single injection

Primary Outcome Measures

Name	Time	Method
relevant biomarkers strongly associated with primary lateralized hyperaldosteronism	30 days after inclusion	* Highest max. standardized uptake value (SUVmax) between both adrenal glands on \[68Ga\]Ga-PTF-PET imaging; * Ratio between SUVmax of both adrenal glands on \[68Ga\]Ga-PTF-PET imaging calculated as highest SUVmax / lowest SUVmax of each adrenal gland; * Difference between SUVmax of both adrenal glands on \[68Ga\]Ga-PTF-PET imaging calculated as the difference highest SUVmax - lowest SUVmax of each adrenal gland; * Ratio between the highest SUVmax among both adrenal glands and mean SUV of the liver on \[68Ga\]Ga-PTF-PET imaging

Secondary Outcome Measures

Name	Time	Method
Lateralization index during AVS	at baseline (during AVS day)
CXCR4 expression levels by immuno-histology highest CXCR4 density	6 months after surgical adrenalectomy	highest CXCR4 density
Aldosterone-to-cortisol ratio between the two adrenal veins on AVS	at inclusion
Incidence of Treatment Emergent Adverse Events after [68Ga]Ga-PentixaFor injection (tolerability)	30 days after [68Ga]Ga-PentixaFor injection	* Adverse events deemed "medically significant" defined by Allergic and anaphylactic reaction ≥ grade 3 according to CTCAE during or following the injection of the radiopharmaceutical * Adverse events of special interest defined by Cutaneous eruption in the three weeks following the injection.
Ratio between the highest SUVmax among both adrenal glands and mean SUV of the liver on [68Ga]Ga-PTF-PET imaging	30 days after inclusion
Proportion of patients with persistence of PA	6 months after surgical adrenalectomy	Patient with a secretion of aldosterone assessed in blood test after surgical adrenalectomy,
Adenoma size on CT	30 days after inclusion
Adenoma size on histology	6 months after surgical adrenalectomy
Incidence of Treatment Emergent Serious Adverse Events after [68Ga]Ga-PentixaFor injection (Safety)	12 months after [68Ga]Ga-PentixaFor injection	- Serious adverse events (any cause).

Locations (2): hôpital Cochin
🇫🇷
Paris, France
Hôpital européen Georges Pompidou - APHP
🇫🇷
Paris, France