Imaging the pharmacokinetics of [F-18]FAU in patients with tumors: PET studies.
OBJECTIVE
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.
Sun
Haihao
H
Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201-2013, USA.
Collins
Jerry M
JM
Mangner
Thomas J
TJ
Muzik
Otto
O
Shields
Anthony F
AF
D001086:Arabinofuranosyluracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003287:Contrast Media / Q000493:pharmacokinetics; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging; D010865:Pilot Projects; D049268:Positron-Emission Tomography / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution
C457880:2'-fluorodeoxyuracil-arabinofuranoside; D003287:Contrast Media; D019788:Fluorodeoxyglucose F18; D001086:Arabinofuranosyluracil