title: Pharmacokinetic Analysis of Dynamic18F-Fluoromisonidazole PET Data in Non-Small Cell Lung Cancer.
abstract: Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies.18F-fluoromisonidazole (18F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of18F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients.Methods:Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static18F-FDG and a dynamic18F-FMISO scan lasting 168±15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered18F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle.Results:We derived average values of18F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate (k3) and delivery rate (K1), influx rate (Ki) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases,k3andKihad a significant strong correlation for all tissue types. The TBR-k3correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally,K1-k3voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R=-0.23±0.39). However, both normal tissue types exhibited significant positive correlations for more than 60% of patients, with 41% having moderate to strong correlations (R>0.5).Conclusion:All lesions showed distinct18F-FMISO uptake. Variable18F-FMISO delivery was observed across lesions, as indicated by the variable values of the kinetic rate constantK1Except for 3 cases, some degree of hypoxia was apparent in all lesions based on their nonzerok3values.
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York schwarj1@mkscc.org.
authors.forename: Jazmin
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Milan
authors.initials: M
authors.lastname: Grkovski
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rimner
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and.
authors.forename: Heiko
authors.initials: H
authors.lastname: Schöder
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Pat B
authors.initials: PB
authors.lastname: Zanzonico
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and.
authors.forename: Sean D
authors.initials: SD
authors.lastname: Carlin
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Staton
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: John L
authors.initials: JL
authors.lastname: Humm
authors.affiliation: National Center for Cancer Care and Research, Doha, Qatar.
authors.forename: Sadek A
authors.initials: SA
authors.lastname: Nehmeh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D008920:Misonidazole
keywords: 18F-fluoromisonidazole; compartmental analysis; hypoxia; non-small cell lung cancer; pharmacokinetic analysis