Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer.
OBJECTIVE
FMAU (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine) is a thymidine analog that can be phosphorylated by thymidine kinase and incorporated into DNA. This first-in-human study of [18F]FMAU was conducted as a pilot in patients to determine its biodistribution and suitability for imaging DNA synthesis in tumors using positron emission tomography (PET).


METHODS
Fourteen patients with diverse cancers (brain, prostate, colorectal, lung, and breast) were imaged with [18F]FMAU. We obtained dynamic PET images for 60 min and a whole-body image. Blood and urine samples were analyzed by high-performance liquid chromatography to measure metabolites and clearance.


RESULTS
Active tumors in the breast, brain, lung and prostate were clearly visualized with standardized uptake values (SUVs) of 2.19, 1.28, 2.21, and 2.27-4.42, respectively. Unlike with other tracers of proliferation, low uptake of [18F]FMAU was seen in the normal bone marrow (SUV(mean) 0.7), allowing visualization of metastatic prostate cancer (SUV 3.07). Low background was also observed in the brain, pelvis, and thorax, aside from heart uptake (SUV 3.36-8.78). In the abdomen, increased physiological uptake was seen in the liver (SUV 10.07-20.88) and kidneys (SUV 7.18-15.66) due to metabolism and/or excretion, but the urinary bladder was barely visible (SUV(mean) 2.03). On average, 95% of the activity in the blood was cleared within 10 min post injection and an average of 70% of the activity in the urine was intact FMAU at 60 min post injection.


CONCLUSIONS
Tumors in the brain, prostate, thorax, and bone can be clearly visualized with FMAU. In the upper abdomen, visualization is limited by the physiological uptake by the liver and kidneys.
Sun
Haihao
H
Karmanos Cancer Institute, Departments of Medicine, Radiology and Pediatrics, Wayne State University, 4100 John R Street, 4 HWCRC, Detroit, MI, 48201-2013, USA.
Sloan
Andrew
A
Mangner
Thomas J
TJ
Vaishampayan
Ulka
U
Muzik
Otto
O
Collins
Jerry M
JM
Douglas
Kirk
K
Shields
Anthony F
AF
D000328:Adult; D000368:Aged; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C034935:clevudine