Ventilation/Perfusion Positron Emission Tomography--Based Assessment of Radiation Injury to Lung.
OBJECTIVE
To investigate (68)Ga-ventilation/perfusion (V/Q) positron emission tomography (PET)/computed tomography (CT) as a novel imaging modality for assessment of perfusion, ventilation, and lung density changes in the context of radiation therapy (RT).


METHODS
In a prospective clinical trial, 20 patients underwent 4-dimensional (4D)-V/Q PET/CT before, midway through, and 3 months after definitive lung RT. Eligible patients were prescribed 60 Gy in 30 fractions with or without concurrent chemotherapy. Functional images were registered to the RT planning 4D-CT, and isodose volumes were averaged into 10-Gy bins. Within each dose bin, relative loss in standardized uptake value (SUV) was recorded for ventilation and perfusion, and loss in air-filled fraction was recorded to assess RT-induced lung fibrosis. A dose-effect relationship was described using both linear and 2-parameter logistic fit models, and goodness of fit was assessed with Akaike Information Criterion (AIC).


RESULTS
A total of 179 imaging datasets were available for analysis (1 scan was unrecoverable). An almost perfectly linear negative dose-response relationship was observed for perfusion and air-filled fraction (r(2)=0.99, P<.01), with ventilation strongly negatively linear (r(2)=0.95, P<.01). Logistic models did not provide a better fit as evaluated by AIC. Perfusion, ventilation, and the air-filled fraction decreased 0.75 ± 0.03%, 0.71 ± 0.06%, and 0.49 ± 0.02%/Gy, respectively. Within high-dose regions, higher baseline perfusion SUV was associated with greater rate of loss. At 50 Gy and 60 Gy, the rate of loss was 1.35% (P=.07) and 1.73% (P=.05) per SUV, respectively. Of 8/20 patients with peritumoral reperfusion/reventilation during treatment, 7/8 did not sustain this effect after treatment.


CONCLUSIONS
Radiation-induced regional lung functional deficits occur in a dose-dependent manner and can be estimated by simple linear models with 4D-V/Q PET/CT imaging. These findings may inform future studies of functional lung avoidance using V/Q PET/CT.
Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. Electronic address: shankar.siva@petermac.org.
Shankar
S
Siva
Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne, Australia; Centre for Medical Radiation Physics, University of Wollongong, Wollongong, Australia.
Nicholas
N
Hardcastle
Department of Physical Sciences, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Tomas
T
Kron
Department of Biostatistics and Clinical Trials, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Mathias
M
Bressel
Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Jason
J
Callahan
Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Michael P
MP
MacManus
Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Mark
M
Shaw
Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Nikki
N
Plumridge
Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Australia; Department of Medicine, University of Melbourne, Parkville, Australia.
Rodney J
RJ
Hicks
Department of Medicine, University of Melbourne, Parkville, Australia; Department of Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Australia.
Daniel
D
Steinfort
Department of Radiation Oncology, Peter MacCallum Cancer Centre, East Melbourne, Australia.
David L
DL
Ball
Centre for Molecular Imaging, Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Australia; Department of Medicine, University of Melbourne, Parkville, Australia.
Michael S
MS
Hofman
D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology / Q000532:radiotherapy*; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D056973:Four-Dimensional Computed Tomography / Q000379:methods; D005710:Gallium Radioisotopes; D006801:Humans; D016014:Linear Models; D008168:Lung / Q000000981:diagnostic imaging / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D011446:Prospective Studies; D017564:Radiation Pneumonitis / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D014692:Ventilation-Perfusion Ratio / Q000528:radiation effects*
D005710:Gallium Radioisotopes