In vivo imaging using positron emission tomography (PET) is important in the development of new radiopharmaceuticals in rodent
animal models for use as biochemical probes, diagnostic agents, or in drug development. We have shown mathematically that, if small
In vivo imaging using positron emission tomography (PET) is important in the development of new radiopharmaceuticals in rodent
animal models for use as biochemical probes, diagnostic agents, or in drug development. We have shown mathematically that, if small
animal imaging studies in rodents are to have the same “quality” as human PET studies, the same number of coincidence events must be
detected from a typical rodent imaging “voxel” as from the human imaging voxel. To achieve this using the same specifi activity
preparation, we show that roughly the same total amount of radiopharmaceutical must be given to a rodent as to a human subject. At high
specifi activities, the mass associated with human doses, when administered to a rodent, may not decrease the uptake of radioactivity at
non saturable sites or sites where an enzyme has a high capacity for a substrate. However, in the case of binding sites of low density such
as receptors, the increased mass injected could saturate the receptor and lead to physiologic effects and non-linear kinetics. Because of the
importance of the mass injected for small animal PET imaging, we experimentally compared high and low mass preparations using ex vivo
biodistribution and phosphorimaging of three compounds: 2-fluoro-2-deoxyglucos (FDG), 6-fluoro-L-metatyrosin (FMT) and one
receptor-directed compound, the serotonin 5HT1A receptor ligand, trans-4-fluoro-N-{2-[4-(2-methoxylphenyl piperazino]ethyl}-N-(2-
pyridyl) cyclohexane- carboxamide (FCWAY). Changes in the mass injected per rat did not affect the distribution of FDG, FMT, and
FCWAY in the range of 0.6 –1.9 nmol per rat. Changes in the target to nontarget ratio were observed for injected masses of FCWAY in
the range of 5–50 nmol per rat. If the specifi activity of such compounds and/or the sensitivity of small animal scanners are not increased
relative to human studies, small animal PET imaging will not correctly portray the “true” tracer distribution. These difficultie will only be
exacerbated in animals smaller than the rat, e.g., mice.[+][-]