11C-methionine PET, a novel method for measuring regional salivary gland function after radiotherapy of head and neck cancer
Introduction
Loss of salivary gland function is a distressing side-effect after radiotherapy (RT) for head and neck cancer [12], caused by incidental irradiation of the major salivary glands. Much recent research has examined whether new techniques of RT spare salivary gland function [6], [18], assessed by stimulated parotid salivary flow measurements. This method, however, is not applicable to the submandibular glands, and it cannot assess function in smaller regions of the salivary glands. 99mTc-pertechnetate SPECT has been proposed for investigating regional parotid gland function after RT [22]. PET is a comparable imaging technique, which enables in vivo studies of human metabolism in 3D, but provides superior spatial resolution than SPECT imaging [17].
The aim of this study was to develop a PET method for measuring regional salivary gland function in the major salivary glands irradiated during RT. For this purpose, we decided to use dynamic PET with the tracer l-[methyl-11C] methionine (11C-methionine). 11C-methionine is a commonly used PET tracer that has been tested for defining tumour volume in head and neck cancer [8], measuring liver protein synthesis [10], [11], and assessing excretory pancreas function [20], [21]. Furthermore, 11C-methionine has been tested for imaging response of head and neck cancer to RT [13], wherein it was noted that salivary gland uptake of 11C-methionine decreased after RT. We hypothesised that regional salivary gland function can be measured by dynamic 11C-methionine PET, and that the PET measure of salivary gland function are reduced dependent on the radiation dose.
To test this hypothesis, dynamic 11C-methionine PET and parotid gland salivary flow measurements were performed in patients with head and neck cancer after RT.
Section snippets
Patients
Eight head and neck cancer patients were included in the study. Two patients were studied before RT, and six patients were studied after minimum 6 months following RT. RT was delivered using either an ipsilateral conformal technique or IMRT for sparing the contralateral parotid gland. Radiation dose to the gross tumour volume was 66–68 Gy in 33–34 fractions over 6 weeks. Elective lymph node areas received 46–50 Gy. All patients except from Patient 5 were treated with the hypoxic radiosensitizer
Results
The sublingual, submandibular, and parotid glands were identified in the summed 11C-methionine PET images. The 11C-radioactivity concentration was consistently higher in salivary glands irradiated with a low radiation dose than in glands irradiated with a high dose (Fig. 1). There was a moderate 11C-radioactivity concentration in the brain and high 11C-radioactivity concentration of the oral and pharyngeal cavity. In specimens of parotid saliva, the 11C-radioactivity concentration was about 300
Discussion
New techniques of RT have enabled sparing of the salivary glands during treatment for head and neck cancer, calling attention to the dose-response relationship of the major salivary glands. For this purpose, we developed a new 3D PET method for measuring regional salivary gland function after RT. Dynamic 11C-methionine PET provides the net metabolic clearance of 11C-methionine as a quantitative measure of regional salivary gland function in the major salivary glands. We found that the net
Acknowledgements
This study was supported by grants from the Danish Medical Research Council (22-02-0337) and the Danish Cancer Society (KFE–Å-235-02). The authors thank Anne Marie Nehen, Department of Neuroradiology P, Aarhus University Hospital for interpreting MR images, and Paul Cumming for critical reading of the manuscript.
References (22)
- et al.
Comparison of radiosensitivity of rat parotid and submandibular glands after different radiation schedules
Radiother Oncol
(2002) - et al.
Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer
Int J Radiat Oncol Biol Phys
(2001) - et al.
Dose, volume, and function relationships in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer
Int J Radiat Oncol Biol Phys
(1999) - et al.
Role of 11-C-methionine positron emission tomography for the delineation of the tumor volume in pharyngo-laryngeal squamous cell carcinoma: comparison with FDG-PET and CT
Radiother Oncol
(2004) Calculation of cerebral glucose phosphorylation from brain uptake of glucose analogs in vivo: a re-examination
Brain Res
(1982)- et al.
Evaluation of response to radiotherapy in head and neck cancer by positron emission tomography and [11C]methionine
Int J Radiat Oncol Biol Phys
(1995) - et al.
Quantitative dose-volume response analysis of changes in parotid gland function after radiotherapy in the head-and-neck region
Int J Radiat Oncol Biol Phys
(2001) - et al.
Feasibility of detecting hypoxia in experimental mouse tumours with 18F-fluorinated tracers and positron emission tomography—a study evaluating [18F]Fluoro-2-deoxy-d-glucose
Acta Oncol
(2000) Role of amino acid transport and countertransport in nutrition and metabolism
Physiol Rev
(1990)- et al.
Labelling and metabolism of methionine-methyl-11 C
Eur J Nucl Med
(1976)