Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmacy

Background:

• Gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) frequently overexpress C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR).
• Accurate staging and therapeutic planning for GEP-NET are crucial, necessitating advanced imaging modalities.

Purpose of the Study:

• To evaluate the feasibility of non-invasive CXCR4-targeted positron emission tomography/computed tomography (PET/CT) imaging using [68Ga]Pentixafor in GEP-NET patients.
• To compare the diagnostic performance of [68Ga]Pentixafor PET/CT with established imaging agents ([68Ga]DOTATOC and [18F]FDG) and immunohistochemistry.

Main Methods:

• Twelve GEP-NET patients (grades G1-G3) underwent PET/CT scans with [68Ga]Pentixafor, [68Ga]DOTATOC, and [18F]FDG.
• Imaging results were correlated with immunohistochemical staining for CXCR4, SSTR2a, and SSTR5.
• Patient and lesion-based analyses were performed to assess sensitivity and specificity.

Main Results:

• [68Ga]DOTATOC detected lesions in 11/12 patients, [18F]FDG in 10/12, and [68Ga]Pentixafor in 6/12.
• SSTR-targeted PET ([68Ga]DOTATOC) was superior for G1 and G2 NET detection.
• [68Ga]Pentixafor PET/CT showed positive tumor visualization in 50% of G2 and 80% of G3 GEP-NET patients, with no detection in G1 NET.

Conclusions:

• CXCR4 expression, visualized by [68Ga]Pentixafor PET/CT, increases with GEP-NET tumor grade.
• While limited for well-differentiated NET, [68Ga]Pentixafor PET/CT may identify advanced, dedifferentiated, SSTR-negative tumors.
• This CXCR4-targeted imaging holds potential for guiding endoradiotherapy selection in specific GEP-NET patient populations.