Investigating the Chemokine Receptor 4 as Potential Theranostic Target in Adrenocortical Cancer Patients

Purpose Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine tumor with limited treatment options. Preclinical studies confirmed overexpression of the chemokine receptor 4 (CXCR4) in this cancer type. This study aimed to analyze the role of CXCR4 imaging using ⁶⁸Ga-pentixafor for ACC staging and selection of patients for CXCR4-directed endoradiotherapy. Methods Thirty patients with histologically proven advanced, metastasized ACC underwent ¹⁸F-FDG PET/CT and ⁶⁸Ga-pentixafor PET/CT within a time interval of 3 ± 4 days to evaluate suitability for CXCR4-directed endoradiotherapy. Scans were analyzed retrospectively for visual extent of ACC and SUV_max/mean of the tumor lesions. ⁶⁸Ga-pentixafor PET was compared with ¹⁸F-FDG PET, the reference imaging standard. All patients were rated for suitability of CXCR4-directed endoradiotherapy considering patient's history, previous treatment, and CXCR4 expression of FDG-positive lesions compared with background activity within the same organ. Results All patients had lesions that were positive for both ¹⁸F-FDG and ⁶⁸Ga-pentixafor PET and were rated as positive for disease. In 2 patients (7%), ⁶⁸Ga-pentixafor PET identified more lesions compared with ¹⁸F-FDG PET. In 5 patients (17%) and 10 patients (33%), complementary and comparable information, respectively, was provided by dual-tracer imaging. In 13 patients (43%), more tumor lesions were identified by ¹⁸F-FDG PET compared with ⁶⁸Ga-pentixafor PET. The ¹⁸F-FDG uptake of the malignant lesions was significantly higher (P < 0.01) than the SUV_max/mean for ⁶⁸Ga-pentixafor. Overall, 70% of the patients were rated as suitable or potentially suitable for CXCR4-directed treatment. Conclusions ⁶⁸Ga-pentixafor allows in vivo imaging of CXCR4 expression in patients with advanced ACC and may serve as companion diagnostic tool in selecting patients for potential CXCR4-directed endoradiotherapy. Seventy percent of the patients with advanced, metastasized ACC may be suitable for a CXCR4-directed treatment after failure of standard treatment options.