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

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.

CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas

“…Especially when considering that CXCR4-directed ERT leads to bone marrow ablation and would require autologous stem cell support [20], the inadequate and heterogenous PET signal suggests that a successful use of this treatment in NEC is very unlikely. However, there is an increasing number of approaches employing 68 Ga-Pentixafor PET/CT to investigate the in vivo CXCR4 expression in other solid tumors like oesophageal cancer or vestibular schwannoma [21,22]. Moreover, Osl et al recently introduced a second generation CXCR4 ligand with potentially improved tumor retention [23].…”

Pentixafor as a Theranostic Agent in Rectal and Pancreatic Adenocarcinoma: Outcomes From a Pilot Study

“…In these studies, correlative immunohistochemical (IHC) studies demonstrated that contributors to CXCR4 expression in tumours included immune cells, stromal elements and tumour cells. Although there was no correlation seen in a small subgroup between tumoral IHC expression of CXCR4 and pentixafor avidity via PET, the infiltrating immune cells were the largest contributor of CXCR4 expression in both a mouse EAC model and a larger collection of human retrospective EAC primaries [32,33]. Consistent with this, pentixafor PET scans in the diagnosis of lymphoid malignancies have shown promise, and in some cases have been more diagnostically sensitive than FDG [34,35].…”

“…Pentixafor has also been investigated in the setting of oesophageal adenocarcinoma in a mouse model of ex vivo autoradiography and pilot studies in humans with oesophageal adenocarcinoma or squamous cell carcinoma. [32,33]. In these studies, correlative immunohistochemical (IHC) studies demonstrated that contributors to CXCR4 expression in tumours included immune cells, stromal elements and tumour cells.…”

Radionuclide imaging and therapy directed towards the tumor microenvironment: a multi-cancer approach for personalized medicine

“…The most successful FC-131-based radioligand is [ 68 Ga]Ga-Pentixafor, which showed superior imaging results compared to [ 18 F]FDG in a clinical pilot study with multiple myeloma patients [181]. In a pilot study with esophageal cancer patients, [ 68 Ga]Ga-Pentixafor imaging was feasible; however, heterogeneous CXCR4 expression limited its application in this cancer type [182]. As Pentixafor does not allow for labeling with therapeutic isotopes, the structurally closely related Pentixather was developed.…”