J Nucl Med 2008 Mar 20;49(3):446-52. Epub 2008 Feb 20.
Department of Nuclear and Radiological Engineering, College of Engineering, University of Florida, Gainesville, Florida 32611-8300, USA.
Unlabelled: The majority of investigational studies of new diagnostic and therapeutic radiopharmaceuticals use murine animal models for preclinical assessments of pharmacokinetics and organ radiation dosimetry. Although mice and rats are widely available and relatively inexpensive, their smaller organ anatomy relative to that of humans can lead to considerable differences in organ dosimetry, thus complicating extrapolations of dose-response relationships to human patients. Nonhuman primates circumvent these problems in many respects but are increasingly becoming expensive and limited because of ethical considerations. With the recent completion of the dog genome project and the recognition of many similarities between canine and human cancers, dogs are increasingly being considered in cancer research and drug development. The main objective of this study was to construct a 3-dimensional computational phantom of a large dog on the basis of whole-body multislice CT data.
Methods: A female hound cross underwent whole-body contrast-enhanced CT at a 2-mm slice thickness. On completion of the scan, the dog was euthanized, and the entire skeleton was harvested for a subsequent microCT investigation. The CT data were imported into a computational software program and used to create a polygon-mesh phantom of the entire animal. All of the major organs and bones were semiautomatically segmented and tagged to the CT slices. The phantom data were imported into a second software program and transformed to a nonuniform rational basis-spline surface phantom, allowing easy alteration of the phantom to simulate dogs of smaller or larger statures. A voxel-based version of the canine phantom was created by use of an in-house routine for subsequent import into the EGSnrc radiation transport code for photon and beta-particle organ dosimetry.
Results: The resulting voxel-based version of the canine phantom had a total body mass of 26.0 kg and a total body tissue mass (exclusive of wall organ content) of 24.5 kg. Although this University of Florida (UF) canine phantom displayed a total body mass intermediate between those of the Oak Ridge National Laboratory (ORNL) 5-y and 10-y stylized human phantoms of the MIRDOSE and OLINDA software codes, considerable differences were noted in organ photon cross-doses. For example, ratios of the specific absorbed fraction Phi(lungs <-- liver)(UF Dog) to Phi(lungs <-- liver)(ORNL 5-y) ranged from approximately 30 at 10 keV to approximately 3.5 at 1 MeV. Corresponding ratios of Phi(lungs <-- liver)(UF Dog) to Phi(lungs <-- liver)(ORNL 10-y) ranged from approximately 6 at 10 keV to approximately 1.3 at 1 MeV. Conversely, values of Phi(kidneys <-- spleen) and Phi(liver <-- spleen) were noted to be much lower (factors of 2-4) and much higher (factors of 2-15), respectively, in the canine phantom than in the ORNL human phantoms. These differences were attributed more to organ shape and position within the torso than to organ mass, because many of the canine organs closely approximated their counterparts volumetrically in the stylized pediatric human phantoms.
Conclusion: The use of canine models, particularly in spontaneously occurring malignancies such as osteosarcoma, for preclinical testing of antineoplastic agents offers significant advantages over current murine models. However, the development of canine-specific technology is critical to the optimization of these studies. The UF canine dosimetry phantom described here aims to solve problems that could stem from the use of current human dosimetry models during radiopharmaceutical research.