Evaluation of tumor hypoxia prior to radiotherapy in intermediate-risk prostate cancer using 18F-fluoromisonidazole PET/CT: a pilot study

Abstract

PurposeHypoxia is a major factor in prostate cancer aggressiveness and radioresistance. Predicting which patients might be bad candidates for radiotherapy may help better personalize treatment decisions in intermediate-risk prostate cancer patients. We assessed spatial distribution of 18F-Misonidazole (FMISO) PET/CT uptake in the prostate prior to radiotherapy treatment.Materials and MethodsIntermediate-risk prostate cancer patients about to receive high-dose (>74 Gy) radiotherapy to the prostate without hormonal treatment were prospectively recruited between 9/2012 and 10/2014. Prior to radiotherapy, all patients underwent a FMISO PET/CT as well as a MRI and 18F-choline-PET. 18F-choline and FMISO-positive volumes were semi-automatically determined using the fuzzy locally adaptive Bayesian (FLAB) method. In FMISO-positive patients, a dynamic analysis of early tumor uptake was performed. Group differences were assessed using the Wilcoxon signed rank test. Parameters were correlated using Spearman rank correlation.ResultsOf 27 patients (median age 76) recruited to the study, 7 and 9 patients were considered positive at 2.5h and 3.5h FMISO PET/CT respectively. Median SUVmax and SUVmax tumor to muscle (T/M) ratio were respectively 3.4 and 3.6 at 2.5h, and 3.2 and 4.4 at 3.5h. The median FMISO-positive volume was 1.1 ml.ConclusionsThis is the first study regarding hypoxia imaging using FMISO in prostate cancer showing that a small FMISO-positive volume was detected in one third of intermediate-risk prostate cancer patients.

Convolutional neural networks for PET functional volume fully automatic segmentation: development and validation in a multi-center setting

“…Finally, the results for all tumors were reviewed and in some cases (< 5%) manually edited before being validated by two experts with more than 15 years of clinical practice. Given that FLAB in such a context has been demonstrated to provide accurate and reliable results in numerous studies [ 11 , 21 , 49 ], including for complex heterogeneous cases [ 17 , 19 ] and over different scanner model and reconstruction algorithms, especially compared to manual delineation [ 18 ], we consider this ground truth sufficiently reliable for the purpose of training and evaluating the proposed approach. Although FLAB was applied only within the manually determined VOI, we then registered the obtained segmentation mask onto the entire PET image used as input to the network for training and testing.…”

18F-FAZA PET imaging in tumor hypoxia: A focus on high-grade glioma

“…As evidenced from the papers analyzed in this review, 18F-FAZA seems to be particularly promising for clinical purposes, with encouraging results regarding the possibility of guiding treatments by adapting treatment in the course of radiotherapy, predicting treatment success in combined radiochemotherapy schemes, or identifying possible tumor regions highly inclined to recurrence. [17][18][19] This radiotracer might also have a role in both treatment planning and monitoring. The possibility to perform hypoxia imaging-guided biopsies could properly represent the vascular heterogeneity within the tumor, being a strong support for planning treatment and predicting patient outcome.…”

Refinement of an Established Procedure and Its Application for Identification of Hypoxia in Prostate Cancer Xenografts

“…The authors suggested that there might not be any correlation between hypoxia and HIF-1α in prostate cancer, but they could not explain the absence of [18F]-FAZA-PET visualization. Supiot and colleagues used another nitroimidazole-derived PET hypoxia-tracer, namely [18F]-FMISO [ 40 ]. In their pilot study, they found that only about 75% of patients with prostate cancer, at any stage, would have [18F]-FMISO-detectable tumors.…”

“…The small sample size in the Garcia-Parra study [ 39 ] could have played a role in their failure to detect [18F]-FAZA-positive tumors. Another factor that could help explain this lack of detection has been suggested [ 40 ] and one that involves an underestimation of [18F]-MISO positive areas because of small volumes of hypoxic areas within the prostate tumors; with current PET-scanning techniques, one cannot map volumes less than a diameter of 3 mm. The use of autoradiography in our study allowed us to detect even small [18F]-FAZA-positive areas within the tumors.…”