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

Abstract:

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).

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1186/s13550-018-0430-4

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Role:
Author
ORCID:
0000-0002-6880-5687
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Oncology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Nuffield Department of Population Health; Clinical Trial Service Unit
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
Oncology
Role:
Author



Publisher:
Springer Open
Journal:
EJNMMI Research More from this journal
Volume:
8
Article number:
73
Publication date:
2018-08-01
Acceptance date:
2018-07-21
DOI:
EISSN:
2191-219X


Keywords:
Pubs id:
pubs:890184
UUID:
uuid:33b569cf-c3fc-4772-b146-387dc241f4a6
Local pid:
pubs:890184
Source identifiers:
890184
Deposit date:
2018-07-22
ARK identifier:

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