PURPOSE: FAU (1-(2'-deoxy-2'-fluoro-beta-D: -arabinofuranosyl) uracil) can be phosphorylated by thymidine kinase, methylated by thymidylate synthase, followed by DNA incorporation and thus functions as a DNA synthesis inhibitor. This first-in-human study of [F-18]FAU was conducted in cancer patients to determine its suitability for imaging and also to understand its pharmacokinetics as a potential antineoplastic agent. METHODS: Six patients with colorectal (n = 3) or breast cancer (n = 3) were imaged with [F-18]FAU. Serial blood and urine samples were analyzed using HPLC to determine the clearance and metabolites. RESULTS: Imaging showed that [F-18]FAU was concentrated in breast tumors and a lymph node metastasis (tumor-to-normal-breast-tissue-ratio 3.7-4.7). FAU retention in breast tumors was significantly higher than in normal breast tissues at 60 min and retained in tumor over 2.5 h post-injection. FAU was not retained above background in colorectal tumors. Increased activity was seen in the kidney and urinary bladder due to excretion. Decreased activity was seen in the bone marrow with a mean SUV 0.6. Over 95% of activity in the blood and urine was present as intact [F-18]FAU at the end of the study. CONCLUSIONS: Increased [F-18]FAU retention was shown in the breast tumors but not in colorectal tumors. The increased retention of FAU in the breast compared to bone marrow indicates that FAU may be useful as an unlabeled antineoplastic agent. The low retention in the marrow indicates that unlabeled FAU might lead to little marrow toxicity; however, the images were not of high contrast to consider FAU for diagnostic clinical imaging.
PURPOSE:FAU (1-(2'-deoxy-2'-fluoro-beta-D: -arabinofuranosyl) uracil) can be phosphorylated by thymidine kinase, methylated by thymidylate synthase, followed by DNA incorporation and thus functions as a DNA synthesis inhibitor. This first-in-human study of [F-18]FAU was conducted in cancerpatients to determine its suitability for imaging and also to understand its pharmacokinetics as a potential antineoplastic agent. METHODS: Six patients with colorectal (n = 3) or breast cancer (n = 3) were imaged with [F-18]FAU. Serial blood and urine samples were analyzed using HPLC to determine the clearance and metabolites. RESULTS: Imaging showed that [F-18]FAU was concentrated in breast tumors and a lymph node metastasis (tumor-to-normal-breast-tissue-ratio 3.7-4.7). FAU retention in breast tumors was significantly higher than in normal breast tissues at 60 min and retained in tumor over 2.5 h post-injection. FAU was not retained above background in colorectal tumors. Increased activity was seen in the kidney and urinary bladder due to excretion. Decreased activity was seen in the bone marrow with a mean SUV 0.6. Over 95% of activity in the blood and urine was present as intact [F-18]FAU at the end of the study. CONCLUSIONS: Increased [F-18]FAU retention was shown in the breast tumors but not in colorectal tumors. The increased retention of FAU in the breast compared to bone marrow indicates that FAU may be useful as an unlabeled antineoplastic agent. The low retention in the marrow indicates that unlabeled FAU might lead to little marrow toxicity; however, the images were not of high contrast to consider FAU for diagnostic clinical imaging.
Authors: Chengyi J Shu; Dean O Campbell; Jason T Lee; Andrew Q Tran; Jordan C Wengrod; Owen N Witte; Michael E Phelps; Nagichettiar Satyamurthy; Johannes Czernin; Caius G Radu Journal: J Nucl Med Date: 2010-06-16 Impact factor: 10.057
Authors: Jing Li; Seongho Kim; Anthony F Shields; Kirk A Douglas; Christopher I McHugh; Jawana M Lawhorn-Crews; Jianmei Wu; Thomas J Mangner; Patricia M LoRusso Journal: J Clin Pharmacol Date: 2016-11 Impact factor: 3.126
Authors: Johannes Schwarzenberg; Caius G Radu; Matthias Benz; Barbara Fueger; Andrew Q Tran; Michael E Phelps; Owen N Witte; Nagichettiar Satyamurthy; Johannes Czernin; Christiaan Schiepers Journal: Eur J Nucl Med Mol Imaging Date: 2010-12-03 Impact factor: 9.236
Authors: Christopher I McHugh; Jawana M Lawhorn-Crews; Dipenkumar Modi; Kirk A Douglas; Steven K Jones; Thomas J Mangner; Jerry M Collins; Anthony F Shields Journal: Cancer Imaging Date: 2016-10-17 Impact factor: 3.909