Validity of Simplified 3′-Deoxy-3′-[18F]Fluorothymidine Uptake Measures for Monitoring Response to Chemotherapy in Locally Advanced Breast Cancer

Mark Lubberink,Jacobus J Van Der Hoeven,Adriaan A Lammertsma,Jasper Emmering,Wieteke Direcks,Otto S Hoekstra,Carla F M Molthoff,Harm Van Tinteren

doi:10.1007/s11307-012-0547-1

Abstract

PurposePositron emission tomography using 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) has been suggested as a means for monitoring response to chemotherapy. The aim of this study was to evaluate the validity of simplified uptake measures for assessing response to chemotherapy using [18F]FLT in locally advanced breast cancer (LABC).ProceduresFifteen LABC patients underwent dynamic [18F]FLT scans both prior to and after the first cycle of chemotherapy with fluorouracil, epirubicin or doxorubicin, and cyclophosphamide. The net uptake rate constant of [18F]FLT, K i, determined by non-linear regression (NLR) of an irreversible two-tissue compartment model was used as the gold standard. In addition to Patlak graphical analysis, standardised uptake values (SUV) and tumour-to-whole blood ratio (TBR) were used for analysing [18F]FLT data. Correlations and relationships between simplified uptake measures and NLR before and after chemotherapy were assessed using regression analysis.ResultsNo significant differences in both pre- and post-chemotherapy relationships between any of the simplified uptake measures and NLR were found. However, changes in SUV between baseline and post-therapy scans showed a significant negative bias and slope less than one, while TBR did not.ConclusionsIn LABC, TBR instead of SUV may be preferred for monitoring response to chemotherapy with [18F]FLT.

Highlights

The positron emission tomography (PET) tracer 3′deoxy-3′-[18F]fluorothymidine ([18F]FLT) [1], a thymidine analogue that is a marker of tumour proliferation, is aThe gold standard for analysing tracer uptake in tissue is by non-linear regression (NLR) of operational equationsM
Data were used from 15 locally advanced breast cancer (LABC) patients participating in an ongoing response monitoring study, the protocol of which was approved by the medical ethics review committee of the VU university medical centre and for which all patients had given written informed consent
Mean whole blood and plasma standardised uptake values (SUV) at 60 min p.i. were significantly lower for post-chemotherapy [18F]FLT scans than for baseline scans (whole blood: mean (SD) SUV 0.57 (0.09) versus 0.61 (0.09), p=0.05, and plasma: mean (SD) SUV 0.66 (0.12) versus 0.72 (0.10), p=0.02)

Summary

Introduction

The positron emission tomography (PET) tracer 3′deoxy-3′-[18F]fluorothymidine ([18F]FLT) [1], a thymidine analogue that is a marker of tumour proliferation, is aThe gold standard for analysing tracer uptake in tissue is by non-linear regression (NLR) of operational equationsM. The positron emission tomography (PET) tracer 3′deoxy-3′-[18F]fluorothymidine ([18F]FLT) [1], a thymidine analogue that is a marker of tumour proliferation, is a. The gold standard for analysing tracer uptake in tissue is by non-linear regression (NLR) of operational equations. In case of [18F]FLT, a two-tissue compartment model is used and, in general, it is assumed that phosphorylated tracer is irreversibly trapped [4,5,6,7,8,9,10]. A good correlation between net uptake rate Ki of [18F]FLT and Ki-67 immunohistochemistry has been shown [2, 11]. Full kinetic analysis is, in principle, the most accurate method for determining net uptake of [18F]FLT, it is relatively complex, at the expense of clinical applicability

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