Targeting CXCR4 with \[68Ga\]Pentixafor: a suitable theranostic approach in pleural mesothelioma?

Our plain-English summary of Targeting CXCR4 with [68Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?, by C. Lapa, S. Kircher, A. Schirbel, et al (Oncotarget, 2017).

The study

• Authors: C. Lapa, S. Kircher, A. Schirbel, A. Rosenwald, S. Kropf, T. Pelzer, T. Walles, A.K. Buck, W.A. Weber, H.J. Wester, K. Herrmann, K. Lückerath
• Journal: Oncotarget
• Published: 2017;8(57):96732-96737
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

C-X-C motif chemokine receptor 4 (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 with positron emission tomography/computed tomography (PET/CT) using [68Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [68Ga]Pentixafor-PET/CT. 2'-[18F]fluoro-2'-deoxy-D-glucose ([18F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [18F]FDG-PET depicted active lesions in all patients, [68Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [68Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.

In plain English

This pilot study tested whether a PET/CT scan using the tracer [68Ga]Pentixafor could show a cell receptor called CXCR4 in pleural mesothelioma. The receptor was being considered as a target for diagnosis and treatment. Six patients (5 males, 1 female, aged 54 to 80) were scanned, and none had been treated at the time of imaging. Four of the six also had a standard [18F]FDG PET/CT scan. Tumor tissue from all six, plus nine further surgical mesothelioma samples, was stained for CXCR4. None of the six patients showed relevant tracer-positive lesions on the Pentixafor scan. Tumor-to-blood ratios were low, with a median of 1.2 for mean values. By contrast, the FDG scans showed active tumor in the patients who had them. None of the tissue samples, from either group, showed CXCR4. The authors concluded that CXCR4 positivity appears less frequent than previously reported. They also noted that only a small number of patients could be included and that most had the epitheloid subtype. The study did not examine asbestos exposure.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: pilot imaging study (feasibility of CXCR4-directed PET/CT) with immunohistochemistry of tumor tissue
• Who was studied: Six patients (5 males, 1 female, aged 54 to 80) with histologically proven pleural mesothelioma, treatment-naive at imaging; 4 of 6 had epitheloid mesothelioma. Also 9 additional surgical mesothelioma samples from patients who were not imaged (epitheloid n = 4, sarcomatoid n = 3, biphasic n = 2; 8 males, 1 female). Location and dates of enrolment not stated.
• Exposure: No asbestos exposure was assessed. The exposure studied was imaging with the CXCR4-targeting tracer [68Ga]Pentixafor (injected activity 78 to 142 MBq), compared with [18F]FDG PET/CT in 4 of 6 patients.
• Main results:
  • None of the six imaged patients showed relevant focal [68Ga]Pentixafor-positive lesions; only normal (physiologic) tracer distribution was seen.
  • Pentixafor tumor-to-blood pool ratios in the six patients were low: median 1.2 (range 0.9 to 1.6) for TBRmean and 1.0 (range 0.7 to 1.4) for TBRmax.
  • [18F]FDG PET identified viable tumor lesions in the patients scanned (4 of 6), with median TBRs of 4.9 (range 2.9 to 5.1) for SUVmean and 5.2 (range 2.5 to 5.8) for SUVmax.
  • Immunohistochemistry of biopsy or surgical tissue from the six imaged patients showed no specific membranous CXCR4 staining.
  • All 9 additional surgical mesothelioma samples from patients who were not imaged were also negative for CXCR4.
• The authors' conclusion: The authors concluded that their data suggest a lower frequency of CXCR4 positivity in pleural mesothelioma than previously reported. They wrote that robust cell surface expression should be confirmed by immunohistochemistry or whole-body [68Ga]Pentixafor-PET/CT before targeting this receptor for therapy.
• Limitations the authors state:
  • Only a small number of patients could be included, so conclusions must be drawn with caution.
  • Most patients and 4 of 9 samples were epitheloid, so differences in CXCR4 expression between histologic subtypes might have been missed.
  • Biopsies were not always taken close in time to PET imaging (maximum interval 4 weeks, with no treatment in between).

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Metastasis, Immunohistochemistry, Biopsy, Mesothelioma.

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• A molecular targeting against nuclear factor-κB, as a chemotherapeutic approach for human malignant mesothelioma — S. Nishikawa, A. Tanaka, et al. (2014)
• One Third of Malignant Pleural Mesothelioma Shows High Immunohistochemical Expression of MSLN or CXCR4 Which Indicates Potent Candidates for Endo-Radiotherapy — T. Hager, S. Borchert, et al. (2023)
• Are circulating microRNAs suitable for the early detection of malignant mesothelioma? Results from a nested case-control study — D.G. Weber, A. Brik, et al. (2019)
• Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma — M.T. Siddiqui, F. Schmitt, et al. (2019)

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