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Radiation Dose Estimates for [18F]5-Fluorouracil Derived from PET-Based and Tissue-Based Methods in Rats

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Abstract

Introduction

Radiation dosimetry assessment often begins with measuring pharmaceutical biodistribution in rodents. The traditional approach to dosimetry in rodents involves a radioassay ex vivo of harvested organs at different time points following administration of the radiopharmaceutical. The emergence of small-animal positron emission tomography (PET) presents the opportunity for an alternative method for making radiodosimetry estimates previously employed only in humans and large animals. In the current manuscript, normal-tissue absorbed dose estimates for the 18F-labeled chemotherapy agent [18F]5-fluorouracil ([18F]5-FU) were derived by PET imaging- and by tissue harvesting-based methods in rats.

Methods

Small-animal PET data were acquired dynamically for up to 2 h after injection of [18F]5-FU in anesthetized rats (n = 16). Combined polynomial and exponential functions were used to model the harvesting-based and imaging-based time–activity data. The measured time–activity data were extrapolated to modeled (i.e., Standard Man) human organs and human absorbed doses calculated.

Results

Organ activities derived by imaging-based and by harvesting-based methods were highly correlated (r > 0.999) as were the projected human dosimetry estimates across organs (r = 0.998) obtained with each method. The tissues calculated to receive highest radiation dose by both methods were related to routes of excretion (bladder wall, liver, and intestines). The harvesting-based and imaging-based methods yielded effective dose (ED) of 2.94E−2 and 2.97E−2 mSv/MBq, respectively.

Conclusions

Small-animal PET presents an opportunity for providing radiation dose estimates with statistical and logistical advantages over traditional tissue harvesting-based methods.

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Acknowledgement

This work is supported by National Institutes of Health/National Cancer Institute, through an ICMIC program grant (project director DHSS).

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Authors and Affiliations

  1. Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, UCLA Medical Center, Los Angeles, CA, USA

    Adam L. Kesner, Wei-Ann Hsueh, Johannes Czernin, Michael E. Phelps & Daniel H. S. Silverman

  2. Siemens Molecular Imaging, Culver City, CA, USA

    Henry Padgett

  3. Nuclear Medicine Clinic, CHS AR-144, UCLA Medical Center, MC694215, Los Angeles, CA, 90095-6942, USA

    Daniel H. S. Silverman

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  1. Adam L. Kesner
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  2. Wei-Ann Hsueh
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  3. Johannes Czernin
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Correspondence to Daniel H. S. Silverman.

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Kesner, A.L., Hsueh, WA., Czernin, J. et al. Radiation Dose Estimates for [18F]5-Fluorouracil Derived from PET-Based and Tissue-Based Methods in Rats. Mol Imaging Biol 10, 341–348 (2008). https://doi.org/10.1007/s11307-008-0160-5

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  • DOI: https://doi.org/10.1007/s11307-008-0160-5

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