Dynamic contrast‐enhanced MRI evaluates the early response of human head and neck tumor xenografts following anti‐EMMPRIN therapy with cisplatin or irradiation

Abstract

Purpose To assess the early therapeutic effects of anti-EMMPRIN antibody with/without cisplatin or X-ray radiation in head and neck cancer mouse models using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Materials and Methods Mice bearing SCC1 (or OSC19) tumor xenografts were treated with anti-EMMPRIN antibody, radiation, cisplatin, or anti-EMMPRIN antibody plus cisplatin (or radiation) for a week (n=4–5 per group). DCE-MRI was carried out on a 9.4T small animal MR scanner on days 0, 3, and 7, and Ktrans values were averaged in 0.5-mm thick peripheral tumor region. Ki67 and CD31 staining were implemented for all tumors after imaging. Results The Ktrans changes of SCC1 and OSC19 tumors treated with anti-EMMPRIN antibody for 3 days were −18±8% and 4±7%, respectively, which were significantly lower than those of control groups (39±5% and 45±7%; p=0.0025 and 0.0220, respectively). When cisplatin was added, those were −42±9% and −44±9%, respectively, and with radiation, −45±9% and −27±10%, respectively, which were also significantly lower than those of control groups (p<0.0001 for all four comparisons). In the eight groups untreated (served as control) or treated with anti-EMMPRIN antibody with/without cisplatin or radiation, the mean Ktrans change for 3 days was significantly correlated with the mean tumor volume change for 7 days (r=0.74, p=0.0346), Ki67 expressing cell density (r=0.96, p=0.0001) and CD31 density (r=0.84, p=0.0084). Conclusion DCE-MRI might be utilized to assess the early therapeutic effects of anti-EMMPRIN antibody with/without chemotherapy or radiotherapy in head and neck cancer.

Functional MRI for the prediction of treatment response in head and neck squamous cell carcinoma: potential and limitations

“…There is less reported research related to intra-treatment monitoring using DCE-MRI compared to DWI possibly because DCE-MRI requires an intravenous injection of a contrast agent. There is some early work in tumour xenografts to suggest a rise in tumour K trans may occur over the first few days of treatment [ 35 ], and in human subjects to suggest a rise in plasma flow at two weeks [ 36 ]. It is postulated that an early rise in K trans is due to damage to the blood vessels causing them to temporarily become leakier, which potentially could increase the delivery of chemotherapeutic agents into the tumour.…”

Prognostic role of diffusion weighted and dynamic contrast-enhanced MRI in loco-regionally advanced head and neck cancer treated with concomitant chemoradiotherapy

“…Dynamic contrast-enhanced MRI (DCE-MRI) can assess the flow of blood through vessels in scanned tissues and therefore enables non-invasive characterization of tumour vascularity and perfusion 12. Due to lack of standardization of data acquisition and analysis12, the results of studies assessing the value of DCE-MRI derived parameters are still scarce and contradictory 13, 14, 15. In addition, studies addressing prognostic values of DCE-MRI parameters acquired early during treatment are lacking.…”

Extracellular vesicles originating from glioblastoma cells increase metalloproteinase release by astrocytes: the role of CD147 (EMMPRIN) and ionizing radiation

“…Moreover, they could reduce the number of local metastases and improve survival with the addition of CD147 antibodies to the radiation treatment. Similarly, Kim et al determined that combining anti-CD147 antibody administration with radiation treatment had a synergistic effect in reducing tumor volume in a head and neck tumor mouse model [46]. Using a small molecule inhibitor, Fu et al showed in vivo that CD147 inhibition decreased progression in a model of metastatic hepatocellular carcinoma [47].…”