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 ), tumorto-blood ratio (T/B) in the late-time image, plasma-to-tissue transport rate (k 1 ), and local vascular volume fraction (b) for head and neck cancer patients. Methods: 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 , b) kinetic parameter images were derived for each patient. Results: 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 b. Data are also presented for other potential hypoxia surrogate measures, for example, k 3 and k 1 /k 2 . Conclusion: 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 b and K i , but no correlation between b and k 1 .

18F-Fluoromisonidazole PET Uptake Is Correlated with Hypoxia-Inducible Factor-1α Expression in Oral Squamous Cell Carcinoma

“…Hypoxia can also induce major changes in gene expression, thereby enhancing the metastatic ability of tumor cells (1). Therefore, intratumoral hypoxia is one of the most important mechanisms promoting tumor aggressiveness, metastasis, and poor prognosis (11).…”

“…Hypoxi a is a common feature of cancer and thus is a prognostic factor for many types of cancer (1,2). Clinically, the prognosis of cancer with low oxygenation levels is poor, and there is strong evidence that this is due to the effects of hypoxia on therapy resistance and malignant progression (2).…”

“…Clinically, the prognosis of cancer with low oxygenation levels is poor, and there is strong evidence that this is due to the effects of hypoxia on therapy resistance and malignant progression (2). In particular, it is clear that hypoxia is a negative factor in the treatment of head and neck cancers, reducing the chance of cure (1). However, it is difficult to determine the conditions of hypoxia in solid tumors.…”

“…18 F-FDG PET is frequently used for the diagnosis and evaluation of treatment outcomes for several tumors. Multiple radiotracers have been developed for hypoxia imaging (1). 18 F-fluoromisonidazole ( 18 F-FMISO) PET is a promising noninvasive method of measuring hypoxia (3)(4)(5)(6).…”

Image-Derived Input Function for Brain PET Studies: Many Challenges and Few Opportunities

“…In addition, several other examples of clinical research protocols using IDIF exist (Beer et al, 2007;Wang et al, 2010). In these studies, IDIF was simply the raw carotid time-activity curve obtained by placing ROIs (regions-of-interest) over the carotid arteries, without any correction for partial volume effect artifacts.…”