In vivo monitoring of the therapeutic efficacy of a CXCR1/2 inhibitor with 18F-FDG PET/CT imaging in experimental head and neck carcinoma: A feasibility study

Abstract

The chemokine receptors CXCR1/2 play a key role in the aggressiveness of several types of cancers including head and neck squamous cell carcinomas (HNSCCs). In HNSCCs, CXCR1/2 signaling promotes cell proliferation and angiogenesis leading to tumor growth and metastasis. The competitive inhibitor of CXCR1/2, C29, inhibits the growth of experimental HNSCCs in mice. However, a non-invasive tool to monitor treatment response is essential to implement the use of C29 in clinical practices. 18 F-FDG PET/CT is a gold-standard tool for the staging and the post-therapy follow-up of HNSCCs patients. Our study aimed to perform the first i n vivo monitoring of C29 efficacy by non-invasive 18 F-FDG PET/CT imaging. Mice bearing experimental HNSCCs (CAL33) were injected with 18 F-FDG (T0) and thereafter treated (n = 7 mice, 9 tumors, 50 mg/kg by gavage) or not (n = 7 mice, 10 tumors) with C29 for 4 consecutive days. Final 18 F-FDG-tumor uptake was determined at day 4 (TF). The average relative change (TF-T0) in 18 F-FDG tumor uptake was +25.85 ± 10.93 % in the control group vs −5.72 ± 10.07 % in the C29-treated group (p < 0.01). These results were consistent with the decrease of the tumor burden and with the decrease of tumor proliferating Ki67+ cells. These results paved the way for the use of 18 F-FDG to monitor tumor response following C29 treatment.

A Potent Solution for Tumor Growth and Angiogenesis Suppression via an ELR+CXCL-CXCR1/2 Pathway Inhibitor

“…22 Similarly, our investigations extended to an HNSCC cell xenograft model, where we were able to monitor therapeutic efficacy using 18 F-FDG PET imaging. 23 Moreover, in a pediatric medulloblastoma model, our compound demonstrated the ability to penetrate within the blood−brain barrier and effectively reduce tumor growth. 24 To further advance our understanding of the structure− activity relationship (SAR) within this compound family and to enhance their efficacy, we designed two series of analogues.…”

“…This effect is accompanied by a down-regulation of AKT phosphorylation and a reduction in CXCL7 and CXCL8 mRNA . Similarly, our investigations extended to an HNSCC cell xenograft model, where we were able to monitor therapeutic efficacy using 18 F-FDG PET imaging . Moreover, in a pediatric medulloblastoma model, our compound demonstrated the ability to penetrate within the blood–brain barrier and effectively reduce tumor growth …”