Heterogeneity in stabilization phenomena in FLT PET images of canines

Abstract

3′-(18F)fluoro-3′-deoxy-L-thymidine (FLT) is a PET marker of cellular proliferation. Its tissue uptake rate is often quantified with a Standardized Uptake Value (SUV), although kinetic analysis provides a more accurate quantification. The purpose of this study is to investigate the heterogeneity in FLT stabilization phenomena. The study was done on 15 canines with spontaneously occurring sinonasal tumours. They were imaged dynamically for 90 min with FLT PET/CT twice; before and during the radiotherapy. Images were analyzed for kinetics on a voxel basis through compartmental analysis. Stabilization curves were calculated as a time-dependant correlation between the time-dependant SUV and the kinetic parameters (voxel values within the tumour were correlated). Stabilization curves were analyzed for stabilization speed, maximal correlation and correlation decrease following the maximal correlation. These stabilization parameters were correlated with the region-averaged kinetic parameters. The FLT SUV was highly correlated with vasculature fraction immediately post-injection, followed by maximum in correlation with the perfusion/permeability. At later times post-injection the FLT SUV was highly correlated (Pearson correlation coefficient above 0.95) with the FLT influx parameter for cases with tumour-averaged SUV30–50min above 2, while others were indeterminate (correlation coefficients from 0.1 to 0.97). All cases with highly correlated SUV and FLT influx parameter had correlation coefficient within 0.5% of its maximum in the period of 30–50 min post-injection. Stabilization time was inversely proportional to the FLT influx rate. Correlation between the FLT SUV and FLT influx parameter dropped at later times post-injection with drop being proportional to the dephosphorylation rate. The FLT was found to be metabolically stable in canines. FLT PET imaging protocol should define minimal and maximal FLT uptake period, which would be 30–50 min for our patients. Additionally, kinetic analysis should be used when low FLT avidity is expected. Low SUVs should be treated with great caution.

Dynamic 18F-FLT PET imaging of spatiotemporal changes in tumor cell proliferation and vasculature reveals the mechanistic actions of anti-angiogenic therapy

“…Relative changes in 18 F-FLT SUVs measured after 20 min post-injection were moderately correlated with relative changes in the proliferative parameter K i . These findings are similar to results from other studies that have assessed the relationship between the 18 F-FLT SUVs and kinetic parameters in greater detail (Muzi et al 2005b, Simoncic andJeraj 2014).…”

Evaluation of 18F-fluorothymidine positron emission tomography ([18F]FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer

“…We therefore, chose to apply this PET parameter to our dataset. [ 18 F]FLT SUV has been shown to be highly correlated to vascular fraction and perfusion/permeability soon after tracer injection [16]. Differences in [ 18 F]FLT delivery, as indicated by AUC 0–1 min , was coincident with treatment response such that patients responding to therapy had a reduction in AUC 0–1 min .…”

“…The percentage change in SUV in both SUV mean and SUV max was then calculated for each target lesion visible on baseline imaging as (SUV post – SUV pre )/SUV pre . The SUV mean time activity curve was used to calculate the area under the curve (AUC) (kg min mL −1 ) from 0 to 1 min, reflecting tracer delivery to the tumour, as intimated in canine studies [16]. The SUVratio, 60:1 (SUV mean 60 min/SUV mean 1 min) was calculated as an indicator of tracer retention within the tumour.…”

Emerging Translational Opportunities in Comparative Oncology With Companion Canine Cancers: Radiation Oncology

“…Comparative canine oncology trials have supported investigations into the kinetics of established and novel PET/CT approaches, as well as characterization of the spatial distribution of these biological markers (63–65). Bradshaw et al concurrently evaluated the predictive value of numerous quantitative imaging biomarkers derived from multitracer PET imaging in tumors before and during RT in dogs with sinonasal tumors (66).…”