Functional Imaging for Early Prediction of Response to Chemoradiotherapy: 3′-deoxy-3′-18F-fluorothymidine Positron Emission Tomography – A Clinical Application Model of Esophageal Cancer

doi:10.1053/j.seminoncol.2006.10.011

Seminars in Oncology

Volume 33, Supplement 11, December 2006, Pages 59-63

https://doi.org/10.1053/j.seminoncol.2006.10.011 Get rights and content

Pathologic complete response after neoadjuvant chemoradiation therapy is associated with increased survival in esophageal cancer. Early detection of response or nonresponse to neoadjuvant chemoradiation might allow individualization of treatment strategies and avoidance of unnecessary treatment. Positron emission tomography (PET) with [¹⁸F]fluorodeoxyglucose (FDG) permits detection of changes in tumor proliferation before any change in tumor size occurs, and FDG-PET findings have been correlated with outcomes in esophageal cancer. However, FDG-PET may fail to distinguish between residual tumor and inflammation and between complete response and partial response with substantial residual tumor burden. PET with the nucleoside analogue 3′-deoxy-3′-¹⁸F-fluorothymidine (FLT) has been found to be more accurate than FDG-PET in visualizing early changes in tumor proliferation. In a recent study in experimental models of esophageal cancer, FLT-PET was more accurate than FDG-PET in detecting early changes in proliferation following docetaxel and radiation therapy in human SEG-1 cells and mouse SEG-1 xenografts, including having a much stronger correlation with histologic findings. Clinical studies are needed to determine if FLT-PET can distinguish among degrees of response to neoadjuvant chemoradiation in patients with esophageal cancer.

Section snippets

Potential Drawbacks to FDG-PET

As noted, FDG-PET uptake after neoadjuvant therapy has been shown to correlate with outcome in esophageal cancer. However, findings also suggest that FDG-PET may not clearly distinguish between residual disease or post-treatment inflammation.6, 7, 8 FDG exhibits considerable accumulation in macrophages and granulation tissues in addition to accumulation in tumor cells,⁷ and may be prone to a fairly high false-positive rate for the use in early detection of response to chemoradiotherapy, which

Potential Advantages of FLT-PET

In contrast to the glucose metabolism exploited in using FDG as a measure of proliferation, the rationale for FLT use is that its monophosphorylation by intracellular tyrosine kinase 1 results in intracellular trapping of the nucleoside analogue. Tyrosine kinase 1 is differentially expressed in the late G₁ and S phases of the cell cycle and is virtually absent in quiescent cells. Experimental and preliminary clinical studies in a number of tumor types have indicated that FLT-PET is a promising

Conclusion

Our study is the first to demonstrate that FLT-PET detects early alterations in tumor cell proliferation after chemoradiation therapy that precede tumor volume change in in vitro and in vivo models of esophageal cancer. FLT uptake declined more rapidly and to a greater extent than FDG uptake in SEG-1 cells in vitro, with the dynamics more closely resembling Thd uptake. Similarly, in xenografts, the T:M uptake ratio for FLT decreased markedly by 48 hours, whereas that for FDG declined to a

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: Supported in part by National Institutes of Health/National Cancer Institute grant nos. CA89198, CA121551, and P50 CA97007.

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Functional Imaging for Early Prediction of Response to Chemoradiotherapy: 3′-deoxy-3′-18F-fluorothymidine Positron Emission Tomography – A Clinical Application Model of Esophageal Cancer

Section snippets

Potential Drawbacks to FDG-PET

Potential Advantages of FLT-PET

Conclusion

Mol Imaging Biol

2-Fluoro-2-deoxy-D-glucose positron emission tomography imaging is predictive of pathologic response and survival after preoperative chemoradiation in patients with esophageal carcinoma

Cancer

Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival

J Clin Oncol

Prediction of response to preoperative chemotherapy in adenocarcinoma of the esophagogastric junction by metabolic imaging

J Clin Oncol

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment

J Clin Oncol

Early detection of chemoradioresponse in esophageal carcinoma by 3′-deoxy-3′-3H-fluorothymidine using preclinical tumor models

Clin Cancer Res

Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography

J Nucl Med

Failure in presumption of residual disease by quantification of FDG uptake in esophageal squamous cell carcinoma immediately after radiotherapy

Radiat Med

Pitfalls of positive findings in staging esophageal cancer with F-18-fluorodeoxyglucose positron emission tomography

Ann Surg Oncol

Functional Imaging for Early Prediction of Response to Chemoradiotherapy: 3′-deoxy-3′-¹⁸F-fluorothymidine Positron Emission Tomography – A Clinical Application Model of Esophageal Cancer

Early detection of chemoradioresponse in esophageal carcinoma by 3′-deoxy-3′-³H-fluorothymidine using preclinical tumor models