Table S1. TAC-by-TAC Wald-Wolfowitz runs-test results for fits of the different models (ticks indicate runs-test passes) (DOCX 38 kb

Bartlomiej Papiez (5581364)

Daniel McGowan (5581358)

Fergus Gleeson (4055239)

Geoff Higgins (4423321)

John Fenwick (5581370)

Julia Schnabel (750247)

Michael Skwarski (5581361)

Ruth Macpherson (5581367)

Background: To determine the relative abilities of compartment models to describe time-courses of 18F-fluoromisonidazole (FMISO) tumour uptake in patients with advanced stage non-small cell lung cancer (NSCLC) imaged using dynamic positron emission tomography (dPET), and study correlations between values of the blood flow-related parameter K1 obtained from fits of the models and an independent blood flow measure obtained from perfusion CT (pCT).   Methods: NSCLC patients had a 45 minute dynamic FMISO PET/CT scan followed by two static PET/CT acquisitions at two and four hours post-injection.  Perfusion CT scanning was then performed consisting of a 45 second cine CT. Reversible and irreversible two-, three- and four-tissue compartment models were fitted to 30 time-activity-curves (TACs) obtained for 15 whole tumour structures in 9 patients, each imaged twice. Descriptions of the TACs provided by the models were compared using the Akaike and Bayesian information criteria (AIC and BIC) and leave-one-out cross-validation. The precision with which fitted model parameters estimated ground-truth uptake kinetics was determined using statistical simulation techniques.  Blood flow from pCT was correlated with K1 from PET kinetic models in addition to FMISO uptake levels. Results: An irreversible three-tissue compartment model provided the best description of whole tumour FMISO uptake time-courses according to AIC, BIC and cross-validation scores totaled across the TACs. The simulation study indicated that this model also provided more precise estimates of FMISO uptake kinetics than other two- and three-tissue models.  The K1 values obtained from fits of the irreversible three-tissue model correlated strongly with independent blood flow measurements obtained from pCT (Pearson r coefficient = 0.81).  The correlation from the irreversible three-tissue model (r=0.81) was stronger than that from than K1 values obtained from fits of a two-tissue compartment model (r=0.68), or FMISO uptake levels in static images taken at time-points from tracer injection through to four hours later (maximum at two minutes, r=0.70). Conclusions: Time-courses of whole tumour FMISO uptake by advanced stage NSCLC are described best by an irreversible three-tissue compartment model.  The K1 values obtained from fits of the irreversible three-tissue model correlated strongly with independent blood flow measurements obtained from perfusion CT (r=0.81)

McGowan, Daniel Robin

Skwarski, Michael

Papiez, Bartlomiej

Macpherson, RE

Gleeson, Fergus

Schnabel, JA

Higgins, Geoffrey

Fenwick, JD

Oxford University Research Archive

English

Whole tumour kinetics analysis of 18F-fluoromisonidazole dynamic PET scans of non-small cell lung cancer patients, and correlations with perfusion CT blood flow

McGowan, DR

Skwarski, M

Papiez, BW

Gleeson, FV

Higgins, GS

Oxford University Research Archive (ORA)

Table S2. Individual AIC, BIC and MSEP scores for fits of the various models to each TAC. The lowest AIC, BIC, and MSEP scores have been underlined for each TAC, indicating the best model according to that measure (DOCX 46 kb

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Additional file 2: of Whole tumor kinetics analysis of 18F-fluoromisonidazole dynamic PET scans of non-small cell lung cancer patients, and correlations with perfusion CT blood flow