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Impact of tissue transport on PET hypoxia quantification in pancreatic tumours

Overview of attention for article published in EJNMMI Research, December 2017
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Title
Impact of tissue transport on PET hypoxia quantification in pancreatic tumours
Published in
EJNMMI Research, December 2017
DOI 10.1186/s13550-017-0347-3
Pubmed ID
Authors

Edward Taylor, Jennifer Gottwald, Ivan Yeung, Harald Keller, Michael Milosevic, Neesha C. Dhani, Iram Siddiqui, David W. Hedley, David A. Jaffray

Abstract

The clinical impact of hypoxia in solid tumours is indisputable and yet questions about the sensitivity of hypoxia-PET imaging have impeded its uptake into routine clinical practice. Notably, the binding rate of hypoxia-sensitive PET tracers is slow, comparable to the rate of diffusive equilibration in some tissue types, including mucinous and necrotic tissue. This means that tracer uptake on the scale of a PET imaging voxel-large enough to include such tissue and hypoxic cells-can be as much determined by tissue transport properties as it is by hypoxia. Dynamic PET imaging of 20 patients with pancreatic ductal adenocarcinoma was used to assess the impact of transport on surrogate metrics of hypoxia: the tumour-to-blood ratio [TBR(t)] at time t post-tracer injection and the trapping rate k 3 inferred from a two-tissue compartment model. Transport quantities obtained from this model included the vascular influx and efflux rate coefficients, k 1 and k 2, and the distribution volume v d ≡k 1/(k 2+k 3). Correlations between voxel- and whole tumour-scale k 3 and TBR values were weak to modest: the population average of the Pearson correlation coefficients (r) between voxel-scale k 3 and TBR (1 h) [TBR(2 h)] values was 0.10 [0.01] in the 20 patients, while the correlation between tumour-scale k 3 and TBR(2 h) values was 0.58. Using Patlak's formula to correct uptake for the distribution volume, correlations became strong (r=0.80[0.52] and r=0.93, respectively). The distribution volume was substantially below unity for a large fraction of tumours studied, with v d ranging from 0.68 to 1 (population average, 0.85). Surprisingly, k 3 values were strongly correlated with v d in all patients. A model was proposed to explain this in which k 3 is a combination of the hypoxia-sensitive tracer binding rate k b and the rate k eq of equilibration in slow-equilibrating regions occupying a volume fraction 1-v d of the imaged tissue. This model was used to calculate the proposed hypoxia surrogate marker k b. Hypoxia-sensitive PET tracers are slow to reach diffusive equilibrium in a substantial fraction of pancreatic tumours, confounding quantification of hypoxia using both static (TBR) and dynamic (k 3) PET imaging. TBR is reduced by distribution volume effects and k 3 is enhanced by slow equilibration. We proposed a novel model to quantify tissue transport properties and hypoxia-sensitive tracer binding in order to improve the sensitivity of hypoxia-PET imaging.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 11 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 11 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 3 27%
Student > Ph. D. Student 3 27%
Professor 1 9%
Student > Bachelor 1 9%
Student > Master 1 9%
Other 1 9%
Unknown 1 9%
Readers by discipline Count As %
Physics and Astronomy 4 36%
Medicine and Dentistry 3 27%
Nursing and Health Professions 1 9%
Psychology 1 9%
Engineering 1 9%
Other 0 0%
Unknown 1 9%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 December 2017.
All research outputs
#10,941,453
of 12,346,626 outputs
Outputs from EJNMMI Research
#155
of 235 outputs
Outputs of similar age
#289,181
of 348,486 outputs
Outputs of similar age from EJNMMI Research
#24
of 28 outputs
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So far Altmetric has tracked 235 research outputs from this source. They receive a mean Attention Score of 1.8. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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