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. 2016 Feb 23;7(8):9288-95.
doi: 10.18632/oncotarget.7063.

[68Ga]Pentixafor-PET/CT for imaging of chemokine receptor 4 expression in small cell lung cancer--initial experience

Constantin Lapa  1 , Katharina Lückerath  1 , Martina Rudelius  2 , Jan-Stefan Schmid  1 , Alexander Schoene  3 , Andreas Schirbel  1 , Samuel Samnick  1 , Theo Pelzer  4 , Andreas K Buck  1 , Saskia Kropf  5 , Hans-Jürgen Wester  6 , Ken Herrmann  1   7
Affiliations

[68Ga]Pentixafor-PET/CT for imaging of chemokine receptor 4 expression in small cell lung cancer--initial experience

Constantin Lapa et al. Oncotarget. .

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.

Keywords: CXCR4; PET; SCLC; molecular imaging; small cell lung cancer.

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Conflict of interest statement

CONFLICTS OF INTEREST

HJW is the founder and shareholder of Scintomics. SK is CEO of Scintomics. All other authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. Example of a CXCR4-positive, SSTR-negative SCLC patient
Display of maximum intensity projections (upper row) and transaxial images (lower row) of both CXCR4- and SSTR-directed PET/CT (interval between both scans, 6 days) in a patient with recurrent SCLC (patient #3). Whereas [68Ga]Pentixafor-PET demonstrates intense tracer retention in various tumor manifestations including mediastinal lymph nodes, bone and pleural lesions, SSTR-directed PET proves negative (arrows; insert: corresponding contrast-enhanced transaxial CT).
Figure 2
Figure 2. Example of additional value of [68Ga]Pentixafor-PET in an SCLC patient
Display of maximum intensity projections (upper row) and transaxial images (lower row) of both CXCR4- and [18F]FDG-PET/CT (interval between both scans, 6 days) in a patient with recurrent SCLC (patient #4). [68Ga]Pentixafor-PET demonstrates more intense tracer retention in various tumor manifestations including mediastinal lymph nodes (arrows; insert: corresponding contrast-enhanced transaxial CT).
Figure 3
Figure 3. Immunohistochemical expression of CXCR4 and somatostatin receptors 2a and 5 in SCLC
Display of two examples of immunohistochemical expression of CXCR4 and SSTR2a and 5, respectively. Patient #3 had his biopsy taken from a lymph node metastasis demonstrating a weak staining for CXCR4 in 90% of the tumor cells (IRS 4). SSTR2a was negative, SSTR5 could also be demonstrated to be weakly expressed in 90% (IRS 4). Patient #9 also presented with extensive disease. Biopsy of the primary tumor revealed mild CXCR4 (intensity 1+ in 70% of the cells, IRS 3) and mild SSTR2a (intensity 1+ in 90%; IRS 4) expression. SSTR5 was negative in the sample. The inserts depict maximum intensity projections are the respective whole-body [68Ga]Pentixafor- and SSTR-directed PET/CT scans, respectively.
See this image and copyright information in PMC

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