Abstract
Chemokine receptor CXCR4 is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging of small cell lung cancer (SCLC) with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [68Ga]Pentixafor.10 patients with primarily diagnosed (n=3) or pre-treated (n=7) SCLC (n=9) or large cell neuroendocrine carcinoma of the lung (LCNEC, n=1) underwent [68Ga]Pentixafor-PET/CT. 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG, n=6) and/or somatostatin receptor (SSTR)-directed PET/CT with [68Ga]DOTATOC (n=5) and immunohistochemistry (n=10) served as standards of reference.CXCR4-PET was positive in 8/10 patients and revealed more lesions with significantly higher tumor-to-background ratios than SSTR-PET. Two patients who were positive on [18F]FDG-PET were missed by CXCR4-PET, in the remainder [68Ga]Pentixafor detected an equal (n=2) or higher (n=2) number of lesions. CXCR4 expression of tumor lesions could be confirmed by immunohistochemistry.Non-invasive imaging of CXCR4 expression in SCLC is feasible. [68Ga]Pentixafor as a novel PET tracer might serve as readout for confirmation of CXCR4 expression as prerequisite for potential CXCR4-directed treatment including receptor-radio(drug)peptide therapy.
Highlights
Small cell lung cancer (SCLC) is a neuroendocrine tumor that represents 15% of all lung cancers [1]
One-third of patients are diagnosed with localized disease, and treatment strategies have focused on systemic therapy [2]
A recent report evaluating biopsy samples of bronchopulmonary neuroendocrine tumors demonstrated a high intensity of CXCR4 receptor expression in SCLC
Summary
Small cell lung cancer (SCLC) is a neuroendocrine tumor that represents 15% of all lung cancers [1]. It occurs predominantly in smokers as almost all patients have a history of tobacco use. SCLC is distinguished clinically from most other types of non-small cell lung cancer by its rapid doubling time, high growth fraction, and the early development of metastases. One-third of patients are diagnosed with localized disease, and treatment strategies have focused on systemic therapy [2]. SCLC is highly responsive to both chemotherapy and radiotherapy, it commonly relapses within months despite treatment [3, 4]. Response rates to second-line treatments have been reported to range between 10-20% [5]. New treatment options www.impactjournals.com/oncotarget including personalized medicine targeting specific molecular markers are urgently needed
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