Multicenter study evaluating extraprostatic uptake of 11 C-choline, 18 F-methylcholine, and 18 F-ethylcholine in male patients: physiological distribution, statistical differences, imaging pearls, and normal variants Athar Haroon a , Lucia Zanoni b , Monica Celli b , Rasoul Zakavi c , Mohsen Beheshti d , Werner Langsteger d , Stefano Fanti b , Mark Emberton a and Jamshed Bomanji a Aim The aim of the study was to evaluate the visceral localization of the three most commonly used choline- based radiotracers ( 11 C-choline, 18 F-methylcholine, and 18 F-ethylcholine) with the aim of analyzing uptake in metabolically and anatomically disease-free patients. Materials and methods A total of 1250 standardized uptake values (SUV max , SUV mean ) were analyzed in 45 anatomical regions in 45 patients (15 patients with 11 C-choline, 15 with 18 F-methylcholine, and 15 with 18 F-ethylcholine). These patients were selected from a cohort of 3721 choline PET/computed tomography studies performed at three teaching hospitals over a period of 10 years. They had no evidence of metabolically active primary disease, metastatic disease, or altered morphology on the computed tomography component of the study or any evidence of disease elsewhere on other imaging modalities. The sites of primary disease (prostate and seminal vesicles) were excluded from evaluation. Results No adverse effect was documented when using the three tracers. Visceral localization was the same for all three tracers. Viscera with a statistical difference in intensity of uptake included the choroid plexus (P = 0.0001), occipital lobe (P = 0.014), parietal lobe (P = 0.008), cerebellum (P = 0.003), parotid gland (P = 0.005), submandibular gland (P = 0.001), tonsils (P = 0.001), thyroid (P = 0.0001), lungs (P = 0.001), aorta (P = 0.001), pulmonary artery (P = 0.0001), liver segments I (P = 0.005), III (P = 0.005), IVB (P = 0.03), and V (P = 0.01), spleen [hilum (P = 0.0009), body (P = 0.0001)], pancreas [head (P = 0.0001), body (P = 0.01), tail (P = 0.002)], esophagus (P = 0.001), stomach (P = 0.0001), duodenum (P = 0.0002), large intestine (P = 0.008), and rectum (P = 0.0001). Elsewhere, no statistical difference was observed. Excreted activity was noted in the kidneys and bladder. Conclusion This study demonstrates that the visceral localization of 11 C-choline, 18 F-methylcholine, and 18 F-ethylcholine in disease-free patients is similar. Depending on the tracer uptake pattern, the viscera can be divided into two distinct categories: those with a statistically significant difference in uptake and those with no difference in uptake. The study outlines the range of SUVs for various organs for the three tracers and identifies some of the potential pitfalls in the evaluation of ‘nonavid’ but clinically significant presentation of different disease entities. Nucl Med Commun 36:1065–1075 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Nuclear Medicine Communications 2015, 36:1065–1075 Keywords: biodistribution, choline, PET/CT, physiological a Department Institute of Nuclear Medicine, T5 University College Hospital, London, UK, b Department of Nuclear Medicine, University Hospital Sant’Orsola Malpighi, Bologna, Italy, c Nuclear Medicine Research Center, Mashad University of Medical Sciences, Mashhad, Iran and d St Vincent’s Hospital, Linz, Austria Correspondence to Jamshed Bomanji, MBBS, MSc, MD, PhD, FRCR, FRCP, Department Institute of Nuclear Medicine, T5 University College Hospital, 235 Euston Road, London NW1 2BU, UK Tel: + 44 0845 155 5000 x70527; fax: + 44 207 380 9407; e-mail: jamshed.bomanji@uclh.nhs.uk Received 24 April 2015 Revised 27 July 2015 Accepted 27 July 2015 Introduction Choline is essential for the biosynthesis of phosphati- dylcholine and other phosphor lipids, which are an inte- gral part of the cell membrane. There is increased cell proliferation in cancer cells, and phospholipid demand increases. This high content can be imaged by PET using choline labeled with 18 F or 11 C. The rate of radio- labeled choline uptake in tumors is an indicator of the tumor cell proliferation rate (in both hypoxia and normoxia), whereas with 18 F-fluorodeoxyglucose ( 18 F-FDG) tumor hypoxia is closely associated with tumor uptake, and radiolabeled choline might detect malignancies ear- lier than the 18 F-FDG [1]. We aimed to evaluate the physiological distribution of the three most commonly used choline-based tracers: 11 C-choline, 18 F-methylcholine, and 18 F-ethylcholine. These tracers have variable bioki- netics and absorption in the body, but to our knowledge this is the first study to evaluate differences in the Original article 0143-3636 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/MNM.0000000000000372 Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.