Investigating the Chemokine Receptor 4 as Potential Theranostic Target in Adrenocortical Cancer Patients.
OBJECTIVE
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.
From the *Department of Nuclear Medicine, †Division of Endocrinology, Department of Internal Medicine I, ‡Comprehensive Cancer Center, and §Department of Radiology, University Hospital of Würzburg, Würzburg; ∥Pharmaceutical Radiochemistry, Technische Universität München, Munich; ¶Scintomics GmbH, Fürstenfeldbruck, Germany; and **Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Christina
C
Bluemel
Stefanie
S
Hahner
Britta
B
Heinze
Martin
M
Fassnacht
Matthias
M
Kroiss
Thorsten A
TA
Bley
Hans-Juergen
HJ
Wester
Saskia
S
Kropf
Constantin
C
Lapa
Andreas
A
Schirbel
Andreas K
AK
Buck
Ken
K
Herrmann
D000306:Adrenal Cortex Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy; D018268:Adrenocortical Carcinoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D056831:Coordination Complexes; D005260:Female; D005710:Gallium Radioisotopes; D006801:Humans; D008187:Lutetium / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010455:Peptides / Q000627:therapeutic use; D010456:Peptides, Cyclic; D000072078:Positron Emission Tomography Computed Tomography; D011868:Radioisotopes / Q000627:therapeutic use; D011877:Radionuclide Imaging; D011878:Radiotherapy; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
C000608226:177Lu-pentixather; C000597686:68Ga-pentixafor; C000608227:90Y-pentixather; C527276:CXCR4 protein, human; D056831:Coordination Complexes; D005710:Gallium Radioisotopes; D010455:Peptides; D010456:Peptides, Cyclic; D011868:Radioisotopes; D019718:Receptors, CXCR4; D015021:Yttrium Radioisotopes; D008187:Lutetium