Sep-Pak analysis is necessary for analyzing serial brain FLT-PET/CT images in glioblastoma multiforme (GBM) patients undergoing treatment

Objectives FLT is a promising biomarker of cell proliferation and early treatment response in a variety of tumor types. Analysis of FLT with only SUV, without FLT metabolite correction and compartmental modeling, may not sufficiently detect changes between serial scans. By 90 minutes post-FLT tracer injection, up to 60% of the 18F-FLT may be metabolized by the liver to 18F-FLT-glucuronide. This inactive, metabolized fraction of FLT must be separated from the active FLT to more accurately assess FLT metabolic flux. We sought to determine whether an average plasma metabolite profile from a population of patients with multiple tumor types pre and post chemoXRT could be accurately applied to individual GBM patients pre and post chemoXRT and whether Sep-Pak analysis from one time point could be applied to the same patient at other serial FLT PET/CT time points.

Methods 9 patients with de novo GBM had 90-min FLT PET/CT brain scans (5 mCi; GE Discovery) at 0, 4-6 wks, and 10 wks after first-line chemoradiation. Sep-Pak plasma analysis was done at 15, 30, and 60 min for 25 of 27 scans.

Results From a population-derived metabolite curve including patients of multiple tumor types and therapy regimens, the metabolite fraction of plasma has previously been shown to be 0.346 at 60 min post FLT injection. The average metabolite fraction for our GBM study group was 21% +/- 4% (range 13-30%). The average change in metabolite fraction in individual patients over three FLT PET/CT studies was 26% +/- 16% (range -46% to +47%.)

Conclusions 1. A population-derived FLT metabolite correction curve cannot be used for accurate model estimation of flux for our GBM patients. 2. A FLT metabolite correction curve at one time point cannot be used for the same patient to correct the blood input function at a different serial time point. 3. The large variance between GBM patients within our study suggests that a population metabolite correction curve may not work for individual GBM patients.

Research Support SNM; GE; BWH Radiology; Friends of the DFCI; NI