Recent Development of CXCR4-Targeted Nuclear Medicine Research in Adrenocortical Tumors

The diagnosis of adrenocortical tumors remains clinically challenging due to overlapping morphological and functional features between benign, malignant, and hormonally active lesions. Malignant and functional tumors are frequently associated with poor prognosis. Traditional morphological imaging methods, such as CT and MRI, cannot reliably distinguish lesion types. Recent evidence suggests that molecular imaging targeting C-X-C motif chemokine receptor 4 (CXCR4), a biomarker overexpressed in functional adenomas and adrenocortical carcinomas (ACC), offers enhanced diagnostic precision. For instance, 68Ga-pentixafor, a CXCR4-targeted radiotracer, demonstrates high accuracy in distinguishing functional from nonfunctional lesions and unilateral from bilateral subtypes in primary aldosteronism. Depending on the level of tracer uptake, it may also be possible to guide therapeutic decisions and assess treatment response. For Cushing's syndrome, particularly cortisol-producing adenomas, CXCR4 imaging facilitates the localization of adrenal lesions, reducing dependency on invasive techniques. In ACC, overexpression of CXCR4 enables metastasis detection, and its complementary use with 18F-FDG PET/CT improves lesion detection. Furthermore, the theranostic agent 177Lu/90Y-Pentixather demonstrates considerable promise for CXCR4-directed Endoradiotherapy (ERT) in advanced ACC. This review aimed to summarize the advancements of CXCR4-targeted molecular imaging in adrenocortical tumors and ERT in ACC.