Analysis and Reproducibility of 3′-Deoxy-3′-[18F]Fluorothymidine Positron Emission Tomography Imaging in Patients with Non–Small Cell Lung Cancer

Abstract

Purpose Imaging tumor proliferation with 3′-deoxy-3′-[18F]fluorothymidine (FLT) and positron emission tomography is being developed with the goal of monitoring antineoplastic therapy. This study assessed the methods to measure FLT retention in patients with non-small cell lung cancer (NSCLC) to measure the reproducibility of this approach. Experimental Design Nine patients with NSCLC who were untreated or had progressed after previous therapy were imaged twice using FLT and positron emission tomography within 2 to 7 days. Reproducibility (that is, error) was measured as the percent difference between the two patient scans. Dynamic imaging was obtained during the first 60 min after injection. Activity in the blood was assessed from aortic images and the fraction of unmetabolized FLT was measured. Regions of interest were drawn on the plane with the highest activity and the adjacent planes to measure standardized uptake value (SUVmean) and kinetic variables of FLT flux. Results We found that the SUVmean obtained from 30 to 60 min had a mean error of 3.6% (range, 0.6–6.9%; SD, 2.3%) and the first and second scans were highly correlated (r2 = 0.99; P < 0.0001). Using shorter imaging times from 25 to 30 min or from 55 to 60 min postinjection also resulted in small error rates; SUVmean mean errors were 8.4% and 5.7%, respectively. Compartmental and graphical kinetic analyses were also fairly reproducible (r2 = 0.59; P = 0.0152 and r2 = 0.58; P = 0.0175 respectively). Conclusion FLT imaging of patients with NSCLC was quite reproducible with a worst case SUVmean error of 21% when using a short imaging time.

Repeatability of 18F-FLT PET in a Multicenter Study of Patients with High-Grade Glioma

“…Kenny et al (4) reported a DSD of 10.5% for SUV mean in breast cancer (n 5 8), which corresponds to an RC of 20.6%. Shields et al (34) used a repeatability metric that is not directly comparable to RC. However, they measured relative differences in SUV mean of up to 21% (non-small cell lung cancer, n 5 9).…”

Monitoring Tumor Response to Therapy with 18F-FLT PET

“…Initial patient studies have further emphasized the potential of 18 F-FLT PET for monitoring tumor response to therapy. 18 F-FLT uptake in untreated tumors has been shown to be stable over time, with a test-retest reproducibility of less than 10% for standardized uptake values when patients were imaged twice within a week (17,18). In 19 patients with recurrent malignant brain tumors treated with irinotecan and bevacizumab, tumor response on 18 F-FLT PET after 1-2 wk of therapy correlated with overall survival at a high level of statistical significance.…”

Nuclear imaging of molecular processes in cancer

“…Accumulation of FLT in proliferating cells reflects increased activity of both nucleoside transporters and thymidine kinase, which traps the tracer by phosphorylation. While FLT is not incorporated into DNA, the cellular uptake of FLT has been shown to correlate with proliferation [31]. The impact of antitumor treatment on FLT uptake is complex and not yet fully understood [32,33].…”