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Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer

  • Molecular Imaging
  • Published:
European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

FMAU (1-(2′-deoxy-2′-fluoro-β-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 (SUVmean 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 (SUVmean 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.

Conclusion

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.

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Acknowledgments

The authors thank Dr. Elizabeth Dawe for veterinary assistance, and Theresa A. Jones, CNMT, for her expert technical assistance in performing the PET studies. This work was partially supported by funding from the National Cancer Institute grants CA 83131 and CA 82645 and the U.S. Department of Defense award W81XWH-04-1-0140.

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Authors and Affiliations

  1. Karmanos Cancer Institute, Departments of Medicine, Radiology and Pediatrics, Wayne State University, 4100 John R Street, 4 HWCRC, Detroit, MI, 48201-2013, USA

    Haihao Sun, Andrew Sloan, Thomas J. Mangner, Ulka Vaishampayan, Otto Muzik, Kirk Douglas & Anthony F. Shields

  2. Food and Drug Administration, Rockville, MD, USA

    Jerry M. Collins

Authors
  1. Haihao Sun
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  2. Andrew Sloan
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  3. Thomas J. Mangner
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  4. Ulka Vaishampayan
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  5. Otto Muzik
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  6. Jerry M. Collins
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  7. Kirk Douglas
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  8. Anthony F. Shields
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Corresponding author

Correspondence to Anthony F. Shields.

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Sun, H., Sloan, A., Mangner, T.J. et al. Imaging DNA synthesis with [18F]FMAU and positron emission tomography in patients with cancer. Eur J Nucl Med Mol Imaging 32, 15–22 (2005). https://doi.org/10.1007/s00259-004-1713-8

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  • DOI: https://doi.org/10.1007/s00259-004-1713-8

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