Diffusion-Weighted Imaging as Predictor of Therapy Response in an Animal Model of Ewing Sarcoma

Reichardt, Wilfried; Juettner, Eva; Uhl, Markus; Elverfeldt, Dominik von; Kontny, Udo

doi:10.1097/rli.0b013e31819dcc84

Cited by 35 publications

(19 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, molecular imaging with DW-MRI is an alternative imaging approach to monitor cancer therapy, as has been shown e.g. for experimental Ewing sarcoma (35). We were unable to detect any substantial differences in tumor ADCmean 1 d or 2 d after a single dose of gemcitabine in either of the lung tumor models investigated here (Fig.…”

Section: Discussionmentioning

confidence: 44%

Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3′-Deoxy-3′-[18F]Fluorothymidine in Preclinical Models of Lung Cancer

et al. 2016

View full text Add to dashboard Cite

3′-Deoxy-3′-[18F]fluorothymidine positron emission tomography ([18F]FLT-PET) and diffusion-weighted MRI (DW-MRI) are promising approaches to monitor tumor therapy response. Here, we employed these two imaging modalities to evaluate the response of lung carcinoma xenografts in mice after gemcitabine therapy. Caliper measurements revealed that H1975 xenografts responded to gemcitabine treatment, whereas A549 growth was not affected. In both tumor models, uptake of [18F]FLT was significantly reduced 6 hours after drug administration. On the basis of the gemcitabine concentration and [18F]FLT excretion measured, this was presumably related to a direct competition of gemcitabine with the radiotracer for cellular uptake. On day 1 after therapy, [18F]FLT uptake was increased in both models, which was correlated with thymidine kinase 1 (TK1) expression. Two and 3 days after drug administration, [18F]FLT uptake as well as TK1 and Ki67 expression were unchanged. A reduction in [18F]FLT in the responsive H1975 xenografts could only be noted on day 5 of therapy. Changes in ADCmean in A549 xenografts 1 or 2 days after gemcitabine did not seem to be of therapy-related biological relevance as they were not related to cell death (assessed by caspase-3 IHC and cellular density) or tumor therapy response. Taken together, in these models, early changes of [18F]FLT uptake in tumors reflected mechanisms, such as competing gemcitabine uptake or gemcitabine-induced thymidylate synthase inhibition, and only reflected growth-inhibitory effects at a later time point. Hence, the time point for [18F]FLT-PET imaging of tumor response to gemcitabine is of crucial importance. Cancer Res; 76(24); 7096–105. ©2016 AACR.

show abstract

Section: Discussionmentioning

confidence: 44%

Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3′-Deoxy-3′-[18F]Fluorothymidine in Preclinical Models of Lung Cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…The analysis of DW imaging data for this application should not be qualitative but rather rely on quantitative changes between the pretreatment and posttreatment images with measurement of the ADCs. Several reports have addressed the utility of DW imaging in the assessment of treatment response and have shown that ADCs correlate well with response in primary bone sarcomas in human patients (36,39,80,113) and in animal models (35,40,43). In soft-tissue sarcomas (18,22,45), ADC changes have been shown to correlate with tumor volume (22) and treatment response (18,45) (Fig 2).…”

Section: Prediction Of Treatment Response Following Neoadjuvant Therapymentioning

confidence: 99%

“…DW imaging has also been used for characterizing changes in the surgical bed in patients examined for evaluation of the possibility of recurrent tumor (23). Furthermore, DW imaging is well suited to the study of a sarcoma after neoadjuvant therapy to determine whether treatment-related necrosis has occurred in a tumor (19,22,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). Where cytotoxic edema develops (eg, in areas of treatment-related necrosis with changes to the dependent sodium-potassium pumps across the cell membrane), there will be increased water mobility, as compared with areas where tumor cellularity is maintained (eg, nonresponsive tumors) (46).…”

Section: Dw Imaging (Functional Technique)mentioning

confidence: 99%

Musculoskeletal Tumors: How to Use Anatomic, Functional, and Metabolic MR Techniques

Jacobs²,

et al. 2012

View full text Add to dashboard Cite

“…The contrast in the resulting images results from differing signal loss from hydrogen proton movement12. DWI has extensively been used in tumor grading34, early detection or differential diagnosis of benign and malignant tumors5678, distinguishing viable and necrotic tissues9101112, assessment of organ function13, prediction of pathologic outcomes1415, and evaluation of tumor response to therapies16171819.…”

mentioning

confidence: 99%

Applicable apparent diffusion coefficient of an orthotopic mouse model of gastric cancer by improved clinical MRI diffusion weighted imaging

Sun

Zhang

et al. 2014

Sci Rep

View full text Add to dashboard Cite

In vivo imaging studies in animal models are hindered by variables that contribute to poor image quality and measurement reliability. As such we sought to improve the diffusion coefficient (ADC) of an orthotopic mouse model of gastric cancer in diffusion-weighted images (DWI) using alginate moulding and Ultrasonic coupling medium. BGC-823 human gastric cancer cells were subcutaneously injected into the abdomen of nude mice and 1 mm3 primary tumour was orthotopically transplanted. Alginate and coupling medium were applied to the mice and MRI (T2 and DWI) was performed for 6 weeks. Regions of interest (ROI) were drawn and liver and tumour ADC were evaluated. Using alginate moulding, the mean quality total score of DW imaging was 8.53; however, in control animals this value was 5.20 (p < 0.001). The coefficient of variation of ADC of liver in experimental and control groups were 0.071 and 0.270 (p < 0.001), respectively, suggesting this method may be helpful for DWI studies of important human diseases such as gastric cancer.

show abstract

Diffusion-Weighted Imaging as Predictor of Therapy Response in an Animal Model of Ewing Sarcoma

Cited by 35 publications

References 26 publications

Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3′-Deoxy-3′-[18F]Fluorothymidine in Preclinical Models of Lung Cancer

Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3′-Deoxy-3′-[18F]Fluorothymidine in Preclinical Models of Lung Cancer

Musculoskeletal Tumors: How to Use Anatomic, Functional, and Metabolic MR Techniques

Applicable apparent diffusion coefficient of an orthotopic mouse model of gastric cancer by improved clinical MRI diffusion weighted imaging

Contact Info

Product

Resources

About