Assessment of Simplified Methods to Measure ¹⁸F-FLT Uptake Changes in EGFR-Mutated Non–Small Cell Lung Cancer Patients Undergoing EGFR Tyrosine Kinase Inhibitor Treatment

Abstract

3′-deoxy-3′-18 F-fluorothymidine ( 18 F-FLT) PET/CT provides a noninvasive assessment of proliferation and, as such, could be a valuable imaging biomarker in oncology. The aim of the present study was to assess the validity of simplified quantitative parameters of 18 F-FLT uptake in non-small cell lung cancer (NSCLC) patients before and after the start of treatment with a tyrosine kinase inhibitor (TKI). Methods: Ten patients with metastatic NSCLC harboring an activating epidermal growth factor receptor mutation were included in this prospective observational study. Patients underwent 15 O-H 2 O and 18 F-FLT PET/CT scanning on 3 separate occasions: within 7 d before treatment, and 7 and 28 d after the first therapeutic dose of a TKI (gefitinib or erlotinib). Dynamic scans were acquired and venous blood samples were collected during the 18 F-FLT scan to measure parent fraction and plasma and whole-blood radioactivity concentrations. Simplified measures (standardized uptake value [SUV] and tumor-to-blood ratio [TBR]) were correlated with fully quantitative measures derived from kinetic modeling. Results: Twenty-nine of thirty 18 F-FLT PET/CT scans were evaluable. According to the Akaike criterion, a reversible 2-tissue model with 4 rate constants and blood volume parameter was preferred in 84% of cases. Relative therapy-induced changes in SUV and TBR correlated with those derived from kinetic analyses (r 2 5 0.83-0.97, P , 0.001, slope 5 0.72-1.12). 18 F-FLT uptake significantly decreased at 7 and 28 d after the start of treatment compared with baseline (P , 0.01). Changes in 18 F-FLT uptake were not correlated with changes in perfusion, as measured using 15 O-H 2 O. Conclusion: SUV and TBR could both be used as surrogate simplified measures to assess changes in 18 F-FLT uptake in NSCLC patients treated with a TKI, at the cost of a small underestimation in uptake changes or the need for a blood sample and metabolite measurement, respectively.

Evaluation of [18F]Fluorothymidine as a Biomarker for Early Therapy Response in a Mouse Model of Colorectal Cancer

“…Similar observations were made in patients with non-small cell lung cancer [23] as well as in mice bearing subcutaneous human epithelial carcinoma and Lewis lung carcinoma tumors [12].…”

“…Since k4 was found to be of the same order of magnitude as k3 (k3/k4 = 0.9 ± 0.3), calculating K FLT was not sensible and only DV tot was considered from the obtained kinetic parameters. SUV mean and TBR mean were calculated from late static [ 18 F]FLT images (70-90 min post-injection) and can be considered as simplified models for irreversible and reversible kinetics, respectively [23]. In this study, DV tot showed a very strong correlation with both static imaging Fig.…”

“…Kinetic modeling of dynamic data is considered to be the most quantitative method since it makes use of a measured arterial input function and a tissue time activity curve. In line with previous studies, the 2TCM with reversible phosphorylation best described the tumor TAC as assessed by the AIC [12,23]. This model, together with an image-derived left ventricular IF, was therefore used to perform all further compartmental analysis.…”

Assessment of Simplified Methods for Quantification of 18F-FDHT Uptake in Patients with Metastatic Castration-Resistant Prostate Cancer

“…All 18 F-FDHT-avid tumors were delineated on an averaged image generated from the last 15 min of the dynamic 18 F-FDHT scan, using a 50% isocontour of SUV peak (sphere of 1.2-cm diameter, positioned to maximize its mean value) corrected for local background to obtain volumes of interest ( Fig. 1) (12). Time-activity curves were produced by projecting tumor volumes of interest on the dynamic 18 F-FDHT and, when applicable, 15 scans by placing a 2 · 2 voxel volume of interest centrally on the ascending aorta in 5 consecutive planes using an early frame in which the blood pool was clearly visible.…”

“…Ordered-subset expectation maximization was used for reconstruction of the images. In addition, during the dynamic 18 F-FDHT scan, 3 manual venous samples were drawn from a separate intravenous cannula at 5, 10, and 30 min after injection (12). For all samples, whole-blood and plasma activity concentrations were measured, as well as parent and metabolite fractions of 18 F-FDHT.…”