Pentixafor PET/CT for imaging of chemokine receptor 4 expression in esophageal cancer - a first clinical approach

Cancer Imaging. 2021 Feb 12;21(1):22. doi: 10.1186/s40644-021-00391-w.

Abstract

Background: Expression of CXCR4, a chemokine (C-X-C motif) receptor that plays a central role in tumor growth and metastasis of circulating tumor cells, has been described in a variety of solid tumors. A high expression of CXCR4 has a prognostic significance with regard to overall and progression-free survival and offers a starting point for targeted therapies. In this context, [68]Ga-Pentixafor-Positron Emission Tomography/Computer Tomography (PET/CT) offers promising possibility of imaging the CXCR4 expression profile. We set out to compare a [18F] fluorodeoxyglucose (FDG)-PET/CT and a [68Ga]Pentixafor-PET/CT in (re-)staging and radiation planning of patients with localized esophageal cancer.

Materials and methods: In this retrospective analysis, ten patients, with adeno- or squamous cell carcinoma of the esophagus (n = 3 and n = 7, respectively), which were scheduled for radio (chemo) therapy, were imaged using both Pentixafor and FDG PET/CT examinations. All lesions were visually rated as Pentixafor and FDG positive or negative. For both tracers, SUVmax was measured all lesions and compared to background. Additionally, immunohistochemistry of CXCR4 was obtained in patients undergoing surgery.

Results: FDG-positive tumor-suspicious lesions were detected in all patients and a total of 26 lesions were counted. The lesion-based analysis brought equal status in 14 lesions which were positive for both tracers while five lesions were FDG positive and Pentixafor negative and seven lesions were FDG negative, but Pentixafor positive. Histopathologic correlation was available in seven patients. The CXCR4 expression of four non-pretreated tumour lesion samples was confirmed immunohistochemically.

Conclusion: Our data shows that additional PET/CT imaging with Pentixafor for imaging the CXCR4 chemokine receptor is feasible but heterogeneous in both newly diagnosed and pretreated recurrent esophageal cancer. In addition, the Pentixafor PET/CT may serve as complementary tool for radiation field expansion in radiooncology.

Keywords: CXCR4; Esophageal cancer; Molecular imaging; PET/CT; Pentixafor; Radiotherapy.

MeSH terms

  • Aged
  • Coordination Complexes / therapeutic use*
  • Esophageal Neoplasms / diagnostic imaging*
  • Female
  • Fluorodeoxyglucose F18 / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Molecular Imaging / methods*
  • Peptides, Cyclic / therapeutic use*
  • Positron Emission Tomography Computed Tomography / methods*
  • Receptors, CXCR4 / metabolism*
  • Retrospective Studies

Substances

  • 68Ga-pentixafor
  • CXCR4 protein, human
  • Coordination Complexes
  • Peptides, Cyclic
  • Receptors, CXCR4
  • Fluorodeoxyglucose F18