GlucoCEST MRI for the Evaluation Response to Chemotherapeutic and Metabolic Treatments in a Murine Triple-Negative Breast Cancer: A Comparison with[18F]F-FDG-PET

Abstract

Triple-negative breast cancer (TNBC) patients have usually poor outcome after chemotherapy and early prediction of therapeutic response would be helpful. [ 18 F]F-FDG-PET/CT acquisitions are often carried out to monitor variation in metabolic activity associated to response to the therapy, despite moderate accuracy and radiation exposure limit its application. The glucoCEST technique relies on the use of unlabelled D-glucose to assess glucose uptake with conventional MRI scanners and is currently under active investigations at clinical level. This work aims at validating the potential of MRI-glucoCEST in monitoring early therapeutic responses in a TNBC tumor murine model. Procedures: Breast tumor (4T1) bearing mice were treated with doxorubicin or dichloroacetate for one week. PET/CT with [ 18 F]F-FDG and MRI-glucoCEST were performed at baseline and after 3 cycles of treatment. Metabolic changes measured with [ 18 F]F-FDG-PET and glucoCEST were compared and evaluated with changes in tumor volumes. Results: Doxorubicin treated mice showed a significant decrease in tumor growth when compared to the control group. GlucoCEST imaging provided early metabolic response after three cycles of treatment, conversely, no variations were detect by in [ 18 F]F-FDG uptake. Dichloroacetate treated mice did not show any decrease either in tumor volume or in tumor metabolic activity as assessed by both glucoCEST and [ 18 F]F-FDG-PET. Conclusions:Early metabolic changes during doxorubicin treatment can be predicted by glucoCEST imaging that appears more sensitive than [ 18 F]F-FDG-PET in reporting on early therapeutic response.These findings support the view that glucoCEST may be a sensitive technique for monitoring metabolic response, but future studies are needed to explore the accuracy of this approach in other tumor types and treatments.

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“…Capozza et al believed that cervical cancer was one of the earliest malignant tumors with clinical staging. Its history could be traced back to 1928 [7]. Reinhold et al believed that the clinical staging classification was born in the context of radiotherapy as the main treatment for cervical cancer [8].…”

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“…Thus, Capozza et al investigated whether the glucoCEST approach can monitor the metabolic response to anticancer therapies in a breast murine cancer model and compared the results with those obtained with the 18 F-FDG-PET approach [ 52 ]. In this study the metastasizing triple negative breast tumor 4T1-bearing mice were treated for two weeks with i) a conventional chemotherapeutic drug (doxorubicin) or ii) with dichloroacetate (DCA) that targets tumor metabolism by reversing the Warburg effect [ 53 ].…”

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“…Doxorubicin treatment resulted in a reduced tumor volume compared with untreated, which was observable 5 d after treatment, and a 1.5% drop in glucoCEST contrast at 14 d after treatment, whereas the FDG-PET is not able to report on any difference (Figure 1C). 26 D-glucose can be metabolized; therefore, analogues of this molecule have been investigated as non-metabolizable alternatives. Rivlin et al considered 3-O-methyl-D-glucose (3OMG), a synthetic non-toxic and non-metabolizable derivative of glucose.…”

“…Doxorubicin treatment resulted in a reduced tumor volume compared with untreated, which was observable 5 d after treatment, and a 1.5% drop in glucoCEST contrast at 14 d after treatment, whereas the FDG‐PET is not able to report on any difference (Figure 1C). 26 …”