[18F]-3′Deoxy-3′-Fluorothymidine Positron Emission Tomography and Breast Cancer Response to Docetaxel

Abstract

Purpose: To establish biomarkers indicating clinical response to taxanes, we determined whether early changes in [18 F]-3 0 deoxy-3 0 -fluorothymidine positron emission tomography (FLT-PET) can predict benefit from docetaxel therapy in breast cancer. Experimental Design: This was a prospective unblinded study in 20 patients with American Joint Committee on Cancer (AJCC) stage II-IV breast cancer unresponsive to first-line chemotherapy or progressing on previous therapy. Individuals underwent a baseline dynamic FLT-PET scan followed by a scan 2 weeks after initiating the first or second cycle of docetaxel. PET variables were compared with anatomic response midtherapy (after 3 cycles).Results: Average and maximum tumor standardized uptake values at 60 minutes (SUV 60,av and SUV 60, max ) normalized to body surface area ranged between 1.7 and 17.0 and 5.6 and 26.9 Â 10 À5 m 2 /mL, respectively. Docetaxel treatment resulted in a significant decrease in FLT uptake (P ¼ 0.0003 for SUV 60,av and P ¼ 0.0002 for SUV 60,max ). Reduction in tumor SUV 60,av was associated with target lesion size changes midtherapy (Pearson R for SUV 60,av ¼ 0.64; P ¼ 0.004) and predicted midtherapy target lesion response (0.85 sensitivity and 0.80 specificity). Decreases in SUV 60,av in responders were due, at least in part, to reduced net intracellular trapping of FLT (rate constant, K i ). Docetaxel significantly reduced K i by 51.1% (AE28.4%, P ¼ 0.0009).Conclusion: Changes in tumor proliferation assessed by FLT-PET early after initiating docetaxel chemotherapy can predict lesion response midtherapy with good sensitivity warranting prospective trials to assess the ability to stop therapy in the event of non-FLT-PET response. Clin Cancer Res; 17(24); 7664-72. Ó2011 AACR.

CNS Metastases in Breast Cancer: Old Challenge, New Frontiers

“…18 F-FLT PET imaging may allow tracking of therapeutic-associated cell-cycle arrest before morphologic changes become measurable. Several studies in breast, lung, and brain tumors have demonstrated that retention of 18 F-FLT correlated with tumor proliferation and have studied it for monitoring early response to therapies (95)(96)(97)(98)(99). Although 18 F-FLT has been used to image and stage several tumor types, the standardized uptake value is generally lower than that obtained with 18 F-FDG (100).…”

Early Determination of Prognosis by Interim 3′-Deoxy-3′-18F-Fluorothymidine PET in Patients with Non-Hodgkin Lymphoma

“…The kinetics of 18 F-FLT uptake in vivo reflect the level of thymidine kinase 1 activity and are thus highly associated with tumor cell proliferation (15). Previous data suggested the possibility of noninvasive tumor grading and early response assessments in patients with malignant diseases (16)(17)(18)(19)(20)(21). The results suggested that 18 F-FLT PET might predict outcomes more precisely than conventional methods in patients with nonHodgkin lymphoma (NHL).…”

Quo Vadis: PET and Single-Photon Molecular Breast Imaging

“…18 F-16a-fluoroestradiol ( 18 F-FES), 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT), and agents imaging progesterone receptors are among several that have been investigated in breast cancer imaging but have not been fully evaluated or Food and Drug Administration-approved. However, as the use of hormonal therapies and phenotyping/prevention increases, it is possible these agents will have greater application and warrant definitive study (45)(46)(47). When used in difficult clinical cases of metastatic breast cancer, information obtained from 18 F-FES PET changed management in nearly half of patients with metastatic breast cancer (47).…”