Hypoxia positron emission tomography imaging: combining information on perfusion and tracer retention to improve hypoxia specificity
Creators: name: Busk, Morten
name: Munk, Ole L.
name: Jakobsen, Steen S.
name: Horsman, Michael R.
Publisher: name: Taylor & Francis
Year: 2019
Subjects: subject: 29999 Physical Sciences not elsewhere classified
subject: FOS: Physical sciences
subject: FOS: Physical sciences
subject: Medicine
subject: Cell Biology
subject: Molecular Biology
subject: Neuroscience
subject: 59999 Environmental Sciences not elsewhere classified
subject: FOS: Earth and related environmental sciences
subject: FOS: Earth and related environmental sciences
subject: Marine Biology
subject: Cancer
subject: 111714 Mental Health
subject: FOS: Health sciences
subject: FOS: Health sciences
subject: Computational Biology

description: <b>Background:</b> Static positron emission tomography (PET) allows mapping of tumor hypoxia, but low resolution and slow tracer retention/clearance results in poor image contrast and the risk of missing areas where hypoxic cells and necrosis are intermixed. Fully dynamic PET may improve accuracy but scan protocols suitable for routine clinical use are warranted. A modeling study proposed that hypoxia specificity can be improved by a clinically feasible blood-flow normalization procedure that only requires a 10- to 15-min dynamic scan (perfusion), followed by a short late static scan, but experimental validation is desired. <b>Methods:</b> Tumor-bearing mice were administered pimonidazole (hypoxia marker) and the PET hypoxia-tracer <sup>18</sup>F-azomycin arabinoside (FAZA) and scanned for 3h. Subsequently, the distributions of FAZA (autoradiography) and hypoxic cells (pimonidazole) were compared on tissue sections. PET images collected in 10-min time intervals between 60 and 90 min post-injection (PET<sub>early</sub>), which mimics the image contrast seen in patients, were compared voxel-by-voxel to 3-h PET (PET<sub>late</sub>). For comparison, PET<sub>early</sub> was normalized to the perfusion peak area, deduced from the first 10 min of the scan (PET<sub>perf</sub>), and the resulting parameter PET<sub>early</sub>/PET<sub>perf</sub> was compared with PET<sub>late</sub>. <b>Results:</b> Tissue analysis revealed a near-perfect spatial match between FAZA signal and hypoxic cell density (pimonidazole) 3 h post-injection, regardless of the tumor type. Only a weak inverse or no correlation between PET<sub>perf</sub> and PET<sub>late</sub> was seen, and the correlation between PET<sub>early</sub>/PET<sub>perf</sub> and PET<sub>late</sub> proved inferior to the correlation between PET<sub>early</sub> and PET<sub>late</sub>. <b>Conclusions:</b> Late PET scans in rodents, unlike patients, provide an accurate map of hypoxia against which earlier time-point scans can be compared. PET<sub>early</sub> and PET<sub>late</sub> correlated to a variable extent but the correlation was lowered by normalization to perfusion (PET<sub>early</sub>/PET<sub>perf</sub>). Our study challenges the validity/robustness of a perfusion normalization approach. This may reflect that the chaotic tumor vasculature uncouples microregional blood flow and oxygen extraction.