Endocrine Abstracts

Introduction: Chemokines are small secreted molecules that promote cell survival, proliferation and directional guidance of migrating cells in normal physiology and tumour pathophysiology. We have recently observed high CXCR4 mRNA expression both in normal human adrenals and in adrenocortical carcinomas. Furthermore, a PET tracer for selective molecular imaging of CXCR4-expression has recently been established.

Objective: To further investigate CXCR4 protein expression in the normal adrenal cortex and in benign adrenocortical tumours and to estimate its potential as a target for molecular imaging in primary hyperaldosteronism (PA).

Methods: CXCR4-expression was evaluated by quantitative PCR and by immunohistochemistry in paraffin-embedded sections of 2 normal adrenals (NA), 117 aldosterone producing adenomas (APA), 49 non-functioning adenomas (NFA), 52 cortisol producing adenomas (CPA). In addition, the expression of its ligand CXCL12 (SDF1), aldosterone synthase and 11-beta-hydroxylase was analyzed using specific antibodies. Furthermore, we performed in vitro binding studies of [68Ga]Pentixafor to frozen tumor tissue of APAs and NAs.

Results: In normal adrenals, strongest CXCR4 staining was found in the outer part of the adrenal cortex covering the CYP11B2 positive zona glomerulosa (ZG) and the outer part of the zona fasciculata while its ligand CXCL12 was particularly expressed in the inner cortical zone. Both qRT-PCR and immunohistochemistry further indicated high CXCR4 expression in most APAs which was significantly higher especially compared NFAs (P=0.01). [68Ga]Pentixafor exhibited strong binding to kryosections of APAs.

Conclusion: The expression pattern of CXCR4 and CXCL12 in normal adrenals suggests that it may play a physiological role in ultrastructural organization of the adrenal cortex. Because of the high expression in APAs compared to CPAs and NFAs and the strong binding of [68Ga]Pentixafor to APAs, CXCR4 may be a suitable target for molecular imaging of APAs in PA.