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

Abstract

We aimed to elucidate the diagnostic potential of the C-X-C motif chemokine receptor 4 (CXCR4)-directed positron emission tomography (PET) tracer 68Ga-Pentixafor in patients with poorly differentiated neuroendocrine carcinomas (NEC), relative to the established reference standard 18F-FDG PET/computed tomography (CT). In our database, we retrospectively identified 11 treatment-naïve patients with histologically proven NEC, who underwent 18F-FDG and CXCR4-directed PET/CT for staging and therapy planning. The images were analyzed on a per-patient and per-lesion basis and compared to immunohistochemical staining (IHC) of CXCR4 from PET-guided biopsies. 68Ga-Pentixafor visualized tumor lesions in 10/11 subjects, while18F-FDG revealed sites of disease in all 11 patients. Although weak to moderate CXCR4 expression could be corroborated by IHC in 10/11 cases, 18F-FDG PET/CT detected significantly more tumor lesions (102 vs. 42; total lesions, n = 107; p < 0.001). Semi-quantitative analysis revealed markedly higher 18F-FDG uptake as compared to 68Ga-Pentixafor (maximum and mean standardized uptake values (SUV) and tumor-to-background ratios (TBR) of cancerous lesions, SUVmax: 12.8 ± 9.8 vs. 5.2 ± 3.7; SUVmean: 7.4 ± 5.4 vs. 3.1 ± 3.2, p < 0.001; and, TBR 7.2 ± 7.9 vs. 3.4 ± 3.0, p < 0.001). Non-invasive imaging of CXCR4 expression in NEC is inferior to the reference standard 18F-FDG PET/CT.

Immunohistochemical expression of chemokine receptor in neuroendocrine neoplasms (CXCR4) of the gastrointestinal tract: a retrospective study of 71 cases

“…Weich et al analyzed the potential of identifying CXCR4-positive NETs providing two different positron emission tomography–computed tomography (PET-CT) methods, one using 68 Ga-Pentixafor and the other using 2-deoxy-2-[fluorine-18]fluoro-D-glucose ( 18 F-FDG). The study concluded that the conventional method using 18 F-FDG identified significant more lesions should be used for imaging CXCR4 assessment [ 19 ].…”

New PET Radiotracers for the Imaging of Neuroendocrine Neoplasms

“…Weich et al described the usefulness of CXCR4-directed imaging with the novel PET tracer [68Ga]Ga-Pentixafor as an alternative to [18F]FDG in poorly differentiated NEC; 11 patients were enrolled (the primary tumour, when identified, was located in the stomach, pancreas, oesophagus, ileum and rectum). [68Ga]Ga-Pentixafor positivity is associated with adverse prognosis, early progression and shortened overall survival [ 48 ••]. In fact, CXCR4 can be considered as a “tumour driver” which regulates the microenvironment and the dissemination of metastasis.…”

Current Status of 68Ga-Pentixafor in Solid Tumours

“…The management of neuroendocrine carcinomas is challenging because most of them present with metastasis and respond poorly to chemotherapy [ 47 ]. There has been interest in identifying other treatment options for patients with poorly differentiated neuroendocrine tumours (NETs) including CXCR4-targeted therapies as strong receptor expression on the tumour cell surface would pave the way for CXCR4-targeted radionuclide therapy in somatostatin receptor (SSTR)-negative patients, given the limited treatment options in de-differentiated NETs.…”