[¹⁸F]AlF-NOTA-pentixather PET/CT of CXCR4 in patients with suspected primary hyperaldosteronism

<b>Background:</b> Distinguishing unilateral aldosterone-producing adenomas (APA) from idiopathic hyperaldosteronism (IHA), nonfunctional adrenal adenoma (NFA), and pheochromocytoma (PHEO) within primary aldosteronism (PA) presents a significant challenge. Studies have demonstrated high levels of chemokine receptor (CXCR) 4 expression in APA, thereby validating the use of ⁶⁸Ga-labeled CXCR4 PET/CT for detecting APA. This study evaluates the efficacy of [¹⁸F]AlF-NOTA-pentixather PET/CT in distinguishing APA from other PA types. <b>Methods:</b> In the initial experiment, a comparative analysis was conducted to evaluate the diagnostic efficacy of [¹⁸F]AlF-NOTA-T140 PET/CT and [¹⁸F]AlF-NOTA-pentixather PET/CT for APA in 3 patients with PA. Based on the preliminary findings, [¹⁸F]AlF-NOTA-pentixather PET/CT was subsequently performed on 45 patients with suspected PA and 5 controls. Lesions exhibiting higher tracer uptake than normal adrenal glands were considered positive and referred for adrenalectomy. Prior to surgery, adrenal venous sampling (AVS) was performed in 71.1% of patients to assess laterality. Postoperative follow-up was conducted in 91.1% of patients. The semi-quantitative analysis involved assessing maximum standardized uptake value (SUVmax), LLR (lesion-to-liver ratio), and lesion-to-contralateral ratio (LCR). Correlations were made between PET/CT findings, histopathology results, outcomes, and AVS. <b>Results:</b> In terms of diagnosing APA, [¹⁸F]AlF-NOTA-pentixather PET/CT demonstrated a sensitivity of 100%, specificity of 91.7%, and accuracy of 95.8%. The mean SUVmax for APAs (25.62 ± 12.71, n = 24) was significantly higher compared to non-APA cases (7.24 ± 3.27, n = 24, <i>P</i> < 0.0001). An optimal SUVmax threshold of 11.60 accurately predicted the presence of APA with a sensitivity of 95.8%, specificity of 96.0%, and accuracy of 93.9%. A cutoff value for LCR at 1.38 provided 95.8% sensitivity and 92.0% specificity, while an LLR cutoff at 5.28 yielded a sensitivity rate of 91.7% and a specificity rate of 92.0%. Positive findings on PET/CT scans were completely consistent with AVS results. All patients with positive lesions derived significant benefits from surgical intervention. <b>Conclusion:</b> [¹⁸F]AlF-NOTA-pentixather PET/CT seems to be highly related to AVS and could be a noninvasive method for diagnosing APA in patients with PA.