Radiotherapy may induce enhanced uptake on F-18-fluoroestradiol PET scans

Introduction: Whole body imaging of 18F-fluoroestradiol (FES) uptake combined with positron emission tomography (PET) has been applied for diagnosis and prediction of therapy response in estrogen receptor (ER) positive breast cancer patients. A maximal standardized uptake value (SUVmax) of 1.5 has previously been defined as the optimal threshold for FES uptake to differentiate between ER-positive and negative tumor lesions. FES uptake in healthy tissue differs per anatomic site and can be influenced by extrinsic factors. Previous FES PET studies have suggested that radiotherapy (RTx) may cause heterogeneous enhanced uptake in lungs. The cause of this uptake has not been elucidated yet. This is an exploratory study to evaluate whether patients with RTx prior to FES PET show enhanced FES uptake in tissues in the irradiation field. Methods: Our FES PET database was screened between 2009 and June 2015 for patients who had RTx ≤6 months before FES PET, independent of location of RTx. Irradiation fields were reconstructed and fused with the FES PET scan. The main outcome was the presence of enhanced FES uptake, defined as visually increased FES uptake above background with a SUVmax >1.5 in the irradiation field in the absence of an oncologic substrate on the concordant (contrast enhanced) CT scan. Results: A total of 133 patients were identified in the database; 29 were eligible for the study. Mean age at the first FES PET scan was 57 (SD 9) years. 28/29 patients had breast cancer, 2/28 had a concurrent other malignancy. Seventeen patients (59%) showed enhanced uptake in the RTx field. 15/17 patients were irradiated in the thoracic area, and 2/17 at the hip. Enhanced uptake was mostly located at the dorsomedial side of the lungs, or subcutaneously after thoracic- or hip RTx, respectively. Patients with normal FES uptake in the radiation field were irradiated in the pelvic/lumbal spine area (n=5), hip (n=3) or thorax (n=4). Time range between RTx and FES PET did not differ between patients with and without enhanced FES uptake (mean 50.9 days [range 0-156] vs. mean 56.8 days [range 0-178]). Systemic treatment at the time of FES PET did not differ between the patients with and without enhanced uptake. Radiation dosage in gray (Gy) was related to enhanced FES uptake, after RTx in the thoracic area or at the hip. Conclusion: RTx can induce enhanced uptake in the irradiation field on the FES PET scan in part of the patients. Irradiation-induced FES uptake most frequently occurs in lung tissue. Therefore, physicians should keep the possibility of radiation-induced aspecific enhanced tracer uptake in mind, when interpreting FES PET scan of patients that have recently received RTx