A comparison of the performance of 68Ga-Pentixafor PET/CT versus adrenal vein sampling for subtype diagnosis in primary aldosteronism

Abstract

Objective: To investigate the diagnostic efficiency and prognostic value of ⁶⁸Ga-Pentixafor PET/CT in comparison with adrenal vein sampling (AVS) for functional lateralization in primary aldosteronism (PA). Histology and long-term clinical follow-up normally serve as the gold standard for such diagnosis.

Methods: We prospectively recruited 26 patients diagnosed with PA. All patients underwent ⁶⁸Ga-Pentixafor PET/CT and AVS. Postsurgical biochemical and clinical outcomes of patients with unilateral primary aldosteronism (UPA), as diagnosed by PET/CT or AVS, were assessed by applying standardized Primary Aldosteronism Surgical Outcome (PASO) criteria. Immunohistochemistry (IHC) was performed to detect the expression of aldosterone synthase (CYP11B2) and CXCR4.

Results: On total, 19 patients were diagnosed with UPA; of these, 13 patients were lateralized by both PET/CT and AVS, four patients were lateralized by PET-only, and two by AVS-only. Seven subjects with no lateralization on AVS and PET received medical therapy. All patients achieved complete biochemical success except one with nodular hyperplasia lateralized by AVS alone. The consistency between PET/CT and AVS outcomes was 77% (20/26). Moreover, CYP11B2-positive nodules were all CXCR4-positive and showed positive findings on PET. Patients who achieved complete biochemical and clinical success had a higher uptake on PET as well as stronger expression levels of CXCR4 and CYP11B2.

Conclusion: Our analysis showed that ⁶⁸Ga-Pentixafor PET/CT could enable non-invasive diagnosis in most patients with PA and identify additional cases of unilateral and surgically curable PA which could not be classified by AVS. ⁶⁸Ga-Pentixafor PET/CT should be considered as a first-line test for the future classification of PA.

Keywords: 68Ga-Pentixafor; CXCR4; PET/CT; endocrine hypertension; primary aldosteronism.

Figure 1

Results of AVS, ⁶⁸Ga-Pentixafor PET/CT and treatment of all patients. AVS, adrenal vein sampling; CT, computed tomography; PET, ⁶⁸Ga-Pentixafor PET/CT.

Figure 2

The performance of ⁶⁸Ga-Pentixafor PET/CT imaging in PA patients. (A, B) show strong and moderate expression separately, as determined by immunohistochemistry with CXCR4 and CYP11B2; positive findings were detected on both AVS and PET/CT scanning (LI, SUVmax; 21.27, 13.01 vs. 8.10, 5.54). (C) A 54-year-old male with bilateral adrenal gland lesions on CT. AVS lateralized the right (LI of 6.73) while PET/CT showed comparable uptake on both sides (SUVmax of R-8.81 and L-7.86). Postoperative pathological examination identified MAPM with weak expression of CXCR4 and CYP11B2. Partial biochemical and clinical success were observed during follow-up. (D) A 60-year-old female with concurrent hypercortisolism. AVS was indefinite (LI of L-1.07 and R-0.93) while PET/CT showed positive finding (SUVmax of 14.42); there was positive expression of CXCR4 and CYP11B2. White arrows indicate the tumor lesion. Magnification ×20 for immunohistochemical staining.

Figure 3

Representative pathological and imaging findings from a 54-year-old male with bilateral adrenal nodules. CT (up) and fusion image (down) in the "Right" column showed slight radioactivity uptake in the right adrenal lesion (1.5 cm × 1.0 cm, SUVmax of 2.86). Left lateralization was identified by ⁶⁸Ga-Pentixafor PET/CT as is shown in the "Left" column (1.5 cm × 1.1 cm, SUVmax of 5.13, LCR of 1.79, LLR of 3.25). AVS showed the same judgment (LI of 3.80). The patient subsequently underwent left adrenalectomy. Immunohistochemistry for CXCR4 (up) and CYP11B2 (down) showing high levels of expression. Follow-up confirmed complete biochemical success. White arrows indicate the tumor lesion. Magnification ×20 for immunohistochemical staining. LCR, ratio of lesional SUVmax to contralateral adrenal SUVmean; LLR, ratio of lesional SUVmax to normal liver SUVmean.

Figure 4

ROC analysis for identifying the dominant side of PA. The AUCs of ROC curves for SUVmax, LCR, LLR and AVS-LI were 0.94 (95% CI, 0.87–1.00), 0.91 (95% CI, 0.79–1.00), 0.99 (95% CI, 0.97–1.00) and 0.89 (95% CI, 0.75–1.00), respectively. To diagnose UPA, the LLR had a higher AUC than other uptake values of PET/CT and AVS-LI. AUC, the area under the ROC curve; AVS-LI, lateralization index based on AVS.

Figure 5

A comparison of ⁶⁸Ga-Pentixafor SUVmax, LCR and LLR values between the complete biochemical and clinical success group and the partial success group for surgery patients (SUVmax of 14.7 ± 2.2 vs. 7.5 ± 1.7; LCR of 3.6 ± 0.5 vs. 1.6 ± 0.2; LLR of 8.6 ± 1.1 vs. 4.2 ± 0.6, respectively, p > 0.05). ns, no significance.

Figure 6

Proportions and absolute numbers (in parentheses) of patients with different prognoses for the three groups by h score (0–4, 5–8, 9–12).