68Ga-Pentixafor PET/CT for Guiding Surgical Treatment of Primary Aldosteronism With Bilateral Adrenal Lesions
Condition: Primary Aldosteronism With Bilateral Adrenal Lesions
MeSH terms: Hyperaldosteronism
Study type: Observational

Summary: 
      Screening potential candidates who may benefit from surgery remains challenging for patients
      diagnosed with primary aldosteronism (PA) accompanied by bilateral adrenal lesions. Although
      adrenal venous sampling is currently the gold standard, it is a technically cumbersome,
      challenging, and difficult-to-interpret invasive procedure that requires a cutting-edge
      facility and radiologists with a high level of expertise, which restricts its widespread use.
      The present study aimed to assess the comprehensive effect of 68Ga-pentixafor positron
      emission tomography/computer tomography (PET/CT) on guiding surgical treatments for PA
      patients with bilateral adrenal lesions.
    

Detailed description: 
      Primary aldosteronism (PA) is characterized by the overproduction of renin-independent
      aldosterone, which results in increased blood volume, potassium excretion, and sodium storage
      in the body, as well as the inhibition of renin-angiotensin system activity. Clinically, the
      condition frequently presents as hypertension and hypokalemia. Patients with PA are at a much
      higher risk of experiencing cardiovascular and cerebrovascular complications than those with
      primary hypertension matched by blood pressure. PA is classified into two subtypes:
      unilateral aldosterone hypersecretion (most often aldosterone-producing adenoma (APA)) and
      contralateral aldosterone non-secretion or bilateral aldosterone hypersecretion (most often
      idiopathic hyperaldosteronism (IHA)). Differentiating PA subtypes is crucial, as patients
      with unilateral adrenal hypersecretion of aldosterone may be cured by the surgical removal of
      the adrenal lesion. Moreover, mineralocorticoid-receptor antagonists (MRAs) are the choice
      therapy for patients with bilateral hypersecretion.

      Computed tomography (CT) is a useful tool for identifying and analyzing abnormalities in the
      adrenal gland and is one of the main methods used to distinguish between unilateral and
      bilateral adrenal lesions. CT images with abnormalities on only one side of the adrenal gland
      in young PA patients (aged <35 years) suggest that abnormal hypersecretion of aldosterone is
      caused by the unilateral adrenal lesion. However, PA patients with bilateral adrenal lesions
      on CT do not necessarily exhibit excessive aldosterone secretion. Aldosterone hypersecretion
      may occur in only one side of the gland. However, because CT does not provide enough
      information about the secretory activity of a detected nodule, it is difficult to distinguish
      the side of the adrenal lesion that secretes excessive aldosterone. In recent years, adrenal
      vein sampling (AVS) - which determines lesions with functional aldosterone secretion - has
      been considered the gold standard for identifying PA subtypes with bilateral adrenal lesions.
      However, the feasibility of AVS remains controversial because of its substantial cost,
      invasiveness with potential risks, and complicated technique with a relatively high rate of
      failure. Therefore, in regions where AVS is infeasible, experienced physicians may recommend
      MRAs treatment directly, or the suspected aldosterone-producing lesions may be removed based
      on the severity of the disease and adrenal CT features. In the latter setting, larger lesions
      or the side of lesions with radiological features of classic cortical adenoma are often
      removed, but these lesions may be non-functional. Therefore, this empirical method has a high
      risk of failure in disease control. Hence, considerable efforts have been made to identify a
      cost-effective, convenient, and non-invasive substitution for AVS. The utilization of
      functional imaging techniques is promising for detecting aldosterone-secreting adrenal
      lesions. For instance, the performance of 11C-metomidate positron emission
      tomography/computer tomography (PET/CT) is comparable to that of AVS. However, the short
      half-life of 11C-metomidate and higher requirements for equipment limits its widespread
      application in clinical practice.

      The C-X-C chemokine receptor 4 (CXCR4) - a G protein-coupled transmembrane receptor - is
      highly expressed in aldosterone-producing tissue16. Its expression is strongly correlated
      with the expression of aldosterone synthase CYP11B2 (cytochrome P450, family, subfamily b,
      polypeptide 2). The utilization of 68Ga-pentixafor, a radiolabeled CXCR4 ligand, enables the
      visualization of tissues exhibiting elevated CXCR4 expression on PET/CT by specifically
      binding to CXCR4 receptors on the cell membrane 18. Evidence has shown that the utilization
      of 68Ga-pentixafor PET/CT in patients with adrenal lesions reveals a notable disparity in the
      uptake value of the tracer between the adrenal lesion side generating excessive aldosterone
      and non-functional adrenal adenomas (NFA). Previous study also showed that 68Ga-pentixafor
      PET/CT has diagnostic significance in PA subtypes. We found that the maximum standardized
      uptake value (SUVmax) of IHA lesions and NFA was significantly lower than that of APA.
      However, studies on the value of PET/CT in patients with PA coupled with bilateral adrenal
      lesions are scanty. Herein, we employed 68Ga-pentixafor PET/CT imaging to evaluate PA
      patients with bilateral adrenal lesions who may receive surgical benefits and tracked their
      prognosis to examine the significance of 68Ga-pentixafor PET/CT in guiding the treatment
      strategy.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        patients with bilateral adrenal lesions who were diagnosed as PA from January 1, 2020, to
        July 1, 2023