Fluorine-18-Labeled Fluoromisonidazole Positron Emission and Computed Tomography-Guided Intensity-Modulated Radiotherapy for Head and Neck Cancer: A Feasibility Study

Abstract

Purpose-Hypoxia renders tumor cells radioresistant, limiting locoregional control from radiotherapy (RT). Intensity-modulated RT (IMRT) allows for targeting of the gross tumor volume (GTV) and can potentially deliver a greater dose to hypoxic subvolumes (GTV h ) while sparing normal tissues. A Monte Carlo model has shown that boosting the GTV h increases the tumor control probability. This study examined the feasibility of fluorine-18-labeled fluoromisonidazole positron emission tomography/computed tomography ( 18 F-FMISO PET/CT)-guided IMRT with the goal of maximally escalating the dose to radioresistant hypoxic zones in a cohort of head and neck cancer (HNC) patients.Methods and Materials-18 F-FMISO was administered intravenously for PET imaging. The CT simulation, fluorodeoxyglucose PET/CT, and 18 F-FMISO PET/CT scans were co-registered using the same immobilization methods. The tumor boundaries were defined by clinical examination and available imaging studies, including fluorodeoxyglucose PET/CT. Regions of elevated 18 F-FMISO uptake within the fluorodeoxyglucose PET/CT GTV were targeted for an IMRT boost. Additional targets and/or normal structures were contoured or transferred to treatment planning to generate 18 F-FMISO PET/CT-guided IMRT plans.Results-The heterogeneous distribution of 18 F-FMISO within the GTV demonstrated variable levels of hypoxia within the tumor. Plans directed at performing 18 F-FMISO PET/CT-guided IMRT for 10 HNC patients achieved 84 Gy to the GTV h and 70 Gy to the GTV, without exceeding the normal tissue tolerance. We also attempted to deliver 105 Gy to the GTV h for 2 patients and were successful in 1, with normal tissue sparing. Conclusion-It was feasible to dose escalate the GTV h to 84 Gy in all 10 patients and in 1 patient to 105 Gy without exceeding the normal tissue tolerance. This information has provided important data for subsequent hypoxia-guided IMRT trials with the goal of further improving locoregional control in HNC patients.

Dose Painting in Radiotherapy for Head and Neck Squamous Cell Carcinoma: Value of Repeated Functional Imaging with18F-FDG PET,18F-Fluoromisonidazole PET, Diffusion-Weighted MRI, and Dynamic Contrast-Enhanced MRI

“…Significant hypoxia was present in 58 patients (79%), and both the degree of hypoxia and the size of the hypoxic volume were independent predictive factors for survival (10). These data imply that 18 F-fluoromisonidazole PET can be used to estimate the burden of hypoxia in HNSCC and can provide a promising target for dose painting (11,12).…”

Fluorodeoxyglucose–Positron-Emission Tomography Imaging of Head and Neck Squamous Cell Cancer

“…33 By accurately defining the GTV with FDG-PET/CT or other potential functional imaging tools such as 18 F-labeled fluoroisonidazole PET/CT, there may be future applications for dose escalation of the GTV to deliver greater tumoricidal doses, while still maintaining adjacent normal tissue within radiation tolerance. 34 The use of PET/CT scanning in radiation planning and contour definition may, however, potentially underestimate tumor volume definition if areas of the tumor demonstrate necrosis or lack of metabolic activity. Thus, it is important to integrate diagnostic information, including contrast-enhanced CT of a PET/DCT or MR imaging, and clinical examination findings into a target definition for radiation planning and not to rely only on 1 imaging tool.…”

The Influence of Changes in Tumor Hypoxia on Dose-Painting Treatment Plans Based on 18F-FMISO Positron Emission Tomography

“…In this regard, a number of radiotracers have been developed and evaluated, including fluorine-18-labeled fluoromisonidazole ( 18 F-FMISO), 18 F-fluoroerythronitroimidazole (21), 18 F-EF5 (22), and 60 Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (23). Recently we have performed PET imaging with 18 F-FMISO (abbreviated as FMISO) in patients with head-and-neck cancer to explore the possibility of applying dose painting to hypoxic regions with IMRT (24,25).…”