Changes in Tumor Biology During Chemoradiation of Cervix Cancer Assessed by Multiparametric MRI and Hypoxia PET

Abstract

PurposeImaging biomarkers assessed with magnetic resonance imaging (MRI) and/or positron emission tomography (PET) enable non-invasive tumor characterization in cervix cancer patients. We investigated the spatio-temporal stability of hypoxia, perfusion, and the cell density of tumors over time by repetitive imaging prior to, during, and after radio-chemotherapy.ProceduresThirteen patients were included in this prospective study. The imaging protocol included the following: [18F]fluoromisonidazole ([18F]FMISO)-PET/x-ray computed tomography (CT) and multiparametric (mp)-MRI at four time-points (TP): baseline (BL); and weeks 2 (TP1), 5 (TP2), and 19 after treatment start (follow-up FU). Complete datasets for six patients could be assessed for tumor volume, enhancement kinetics, diffusivity, and [18F]FMISO-avidity (P1–P6). In addition, two patients completed all PET/CT examinations (P7–P8) but not all MR scans; however, one of them had no hypoxia (P8). Descriptive statistics, correlations, and voxel-by-voxel analysis were performed. For various, independent reasons, five patients could not complete the study according to the protocol with all imaging sequences.ResultsMedian tumor ADCs (in ×10−3 mm2/s) were 0.99 ± 0.10 at BL, 1.20 ± 0.12 at TP1, 1.33 ± 0.14 at TP2, and 1.38 ± 0.21 at FU. The median TBRpeak (tumor-to-background) was 2.7 ± 0.8 at BL, 1.6 ± 0.2 at TP1, 1.8 ± 0.3 at TP2, and 1.7 ± 0.3 at FU. The voxel-by-voxel analysis of the [18F]FMISO uptake at BL and TP1 showed no correlation. Between TP2 and TP1 and FU and TP2, weak correlations were found for two patients.ConclusionsLongitudinal mp-MR and PET imaging enables the in vivo tumor characterization over time. While perfusion and cell density decreased, there was a non-uniform change of hypoxia observed during radiotherapy. To assess the potential impact with regard to more personalized treatment approaches, hypoxia imaging-based dose painting for cervix cancer requires further research.

Hypoxia Imaging and Biological Evaluation of the Radiosensitizing Effect of Oleanolic Acid

“…18 F-FMISO is a nitroimidazole compound radiolabeled with 18 F which should accumulate in hypoxic tissue and wash out quickly from normoxic tissue [ 11 ]. 18 F-FMISO has been widely used as a PET imaging tracer of hypoxia [ 12 ]. Compared with 18 F-FDG, the signal of 18 F-FMISO in tumors is lower.…”

Penalized maximum likelihood simultaneous longitudinal PET image reconstruction with difference‐image priors

“…One of the most important examples of such longitudinal PET protocols is in cancer imaging, where the response of a tumor to a treatment is often of interest . Within this area, multiple PET scans are used for a wide range of purposes such as predicting treatment response, guiding future treatment, or assessing the efficacy of new biomarkers in reflecting tumor response . Such studies have been performed for various cancer treatments, such as chemotherapy, radiotherapy, and immunotherapy .…”

“…Analysis of longitudinal changes throughout these image series is also varied, ranging from qualitative methods, through semiquantitative measures like standardized uptake values (SUVs), to full quantitation of tumor metabolism, for example, by Patlak analysis . Reported SUVs include the maximum SUV measured within the tumor, the mean value within the tumor, and in some cases the SUV is compared to a background region such as the liver for increased stability …”

“…1 Within this area, multiple PET scans are used for a wide range of purposes such as predicting treatment response, 2 guiding future treatment, 3 or assessing the efficacy of new biomarkers in reflecting tumor response. 4 Such studies have been performed for various cancer treatments, such as chemotherapy, 5 radiotherapy, 6 and immunotherapy. 7 The number of scans that are performed in longitudinal oncological protocols varies greatly; although two to five scans are typical, 8,2,6 more than 10 can be acquired in specific contexts.…”

“…8,9 Reported SUVs include the maximum SUV measured within the tumor, 5 the mean value within the tumor, 6 and in some cases the SUV is compared to a background region such as the liver for increased stability. 4,7 For the majority of these longitudinal PET studies, images are typically reconstructed with iterative reconstruction methods such as maximum likelihood expectationmaximization (MLEM) 10 or, more commonly, an accelerated version of MLEM known as ordered subsets expectation-maximization, or OSEM. 11 Iterative methods can produce PET images that are superior in quality to analytic methods such as filtered back-projection (FBP) by incorporating more realistic models of the acquisition process and by taking into account the Poisson distributed nature of the acquired counts.…”