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Background  To determine the relative abilities of compartment models to describe time-courses of 18F-fluoromisonidazole (FMISO) tumor 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  K  1  obtained from fits of the models and an independent blood flow measure obtained from perfusion CT (pCT).  NSCLC patients had a 45-min dynamic FMISO PET/CT scan followed by two static PET/CT acquisitions at 2 and 4-h post-injection. Perfusion CT scanning was then performed consisting of a 45-s cine CT.  Reversible and irreversible two-, three- and four-tissue compartment models were fitted to 30 time-activity-curves (TACs) obtained for 15 whole tumor 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  K  1  from PET kinetic models in addition to FMISO uptake levels.    Results  An irreversible three-tissue compartment model provided the best description of whole tumor 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  K  1  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  K  1  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 4 h later (maximum at 2 min,  r  = 0.70).    Conclusions  Time-courses of whole tumor FMISO uptake by advanced stage NSCLC are described best by an irreversible three-tissue compartment model. The  K  1  values obtained from fits of the irreversible three-tissue model correlated strongly with independent blood flow measurements obtained from perfusion CT ( r  = 0.81).    Electronic supplementary material  The online version of this article (10.1186/s13550-018-0430-4) contains supplementary material, which is available to authorized users.

ejnmmi research

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