Pharmacokinetic Analysis of Hypoxia 18F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer

Abstract

This study used pharmacokinetic analysis of (18)F-labeled fluoromisonidazole ((18)F-FMISO) dynamic PET to assist the identification of regional tumor hypoxia and to investigate the relationship among a potential tumor hypoxia index (K(i)), tumor-to-blood ratio (T/B) in the late-time image, plasma-to-tissue transport rate (k(1)), and local vascular volume fraction (beta) for head and neck cancer patients. Newly diagnosed patients underwent a dynamic (18)F-FMISO PET scan before chemotherapy or radiotherapy. The data were acquired in 3 consecutive PET/CT dynamic scan segments, registered with each other and analyzed using pharmacokinetics software. The (K(i), k(1), beta) kinetic parameter images were derived for each patient. Nine patients' data were analyzed. Representative images of (18)F-FDG PET (of the tumor), CT (of the anatomy), and late-time (18)F-FMISO PET (of the T/B) and parametric images of K(i) (potentially representing tumor hypoxia) are shown. The patient image data could be classified into 3 types: with good concordance between the parametric hypoxia map K(i) and high T/B, with concordant findings between the parametric hypoxia map and low T/B, and with ambiguity between parametric hypoxia map and T/B. Correlation coefficients are computed between each pair of T/B, K(i), k(1), and beta. Data are also presented for other potential hypoxia surrogate measures, for example, k(3) and k(1)/k(2). There is a positive correlation of 0.86 between the average T/B and average hypoxia index K(i) of the region of interest. However, because of the statistical photon counting noise in PET and the amplification of noise in kinetic analysis, the direct correlation between the T/B and hypoxia of the individual pixel is not obvious. For a tumor region of interest, there is a slight negative correlation between k(1) and K(i), moderate positive correlation between beta and K(i), but no correlation between beta and k(1).