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

Abstract

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 Ga-pentixafor for ACC staging and selection of patients for CXCR4-directed endoradiotherapy.

METHODS:

Thirty patients with histologically proven advanced, metastasized ACC underwent F-FDG PET/CT and Ga-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 SUVmax/mean of the tumor lesions. Ga-pentixafor PET was compared with F-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 F-FDG and Ga-pentixafor PET and were rated as positive for disease. In 2 patients (7%), Ga-pentixafor PET identified more lesions compared with F-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 F-FDG PET compared with Ga-pentixafor PET. The F-FDG uptake of the malignant lesions was significantly higher (P < 0.01) than the SUVmax/mean for Ga-pentixafor. Overall, 70% of the patients were rated as suitable or potentially suitable for CXCR4-directed treatment.

CONCLUSIONS:

Ga-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.

• Authors: Christina Bluemel, Stefanie Hahner, Britta Heinze, Martin Fassnacht, Matthias Kroiss, Thorsten A Bley, Hans-Juergen Wester, Saskia Kropf, Constantin Lapa, Andreas Schirbel, Andreas K Buck, Ken Herrmann
• Journal: Clinical nuclear medicine (Clin Nucl Med) Vol. 42 Issue 1 Pg. e29-e34 (Jan 2017) ISSN: 1536-0229 [Electronic] United States
• PMID: 27819856 (Publication Type: Journal Article)

Chemical References

• 177Lu-pentixather
• 68Ga-pentixafor
• 90Y-pentixather
• CXCR4 protein, human
• Coordination Complexes
• Gallium Radioisotopes
• Peptides
• Peptides, Cyclic
• Radioisotopes
• Receptors, CXCR4
• Yttrium Radioisotopes
• Lutetium

Topics

• Adrenal Cortex Neoplasms (diagnostic imaging, metabolism, radiotherapy)
• Adrenocortical Carcinoma (diagnostic imaging, metabolism, radiotherapy)
• Adult
• Aged
• Coordination Complexes
• Female
• Gallium Radioisotopes
• Humans
• Lutetium (therapeutic use)
• Male
• Middle Aged
• Patient Selection
• Peptides (therapeutic use)
• Peptides, Cyclic
• Positron Emission Tomography Computed Tomography
• Radioisotopes (therapeutic use)
• Radionuclide Imaging
• Radiotherapy
• Receptors, CXCR4 (metabolism)
• Yttrium Radioisotopes (therapeutic use)