Log normal distribution of cellular uptake of radioactivity: implications for biologic responses to radiopharmaceuticals.
It is widely recognized that radiopharmaceuticals are generally distributed nonuniformly in tissues. Such nonuniformities are observed over the entire range of spatial levels, ranging from organ to subcellular levels. The implications of nonuniform distributions of radioactivity for dosimetry, and ultimately for the biologic response of tissues containing radioactivity, have been investigated extensively. However, there is a paucity of experimental data on the distribution of cellular activity within a population of cells. In the present study, the distribution of activity per cell is experimentally determined and its implications for predicting biologic response are examined.


METHODS
Chinese hamster V79 cells were exposed to different concentrations of (210)Po-citrate. The radiolabeled cells were washed, seeded into culture dishes or glass slides, covered with photographic emulsion, and stored in an opaque container. Subsequently, the emulsion was developed, thereby resulting in observable alpha-particle tracks that were scored.


RESULTS
The distribution of activity per cell was found to be well described by a log normal distribution function. Theoretic modeling of cell survival as a function of mean activity per cell showed that survival curves differed substantially when the activity per cell was log normally distributed versus when it was assumed conventionally that every cell in the population contained the mean activity.


CONCLUSIONS
The present study provides experimental evidence of log normal cellular uptake of radioactivity. Theoretic calculations show that a log normal distribution of cellular activity can have a substantial impact on modeling the biologic response of cell populations.
Neti
Prasad V S V
PV
Division of Radiation Research, Department of Radiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, USA.
Howell
Roger W
RW
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D015233:Models, Statistical; D016011:Normal Distribution; D011059:Polonium / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011829:Radiation Dosage; D011874:Radiometry; D012062:Relative Biological Effectiveness; D013347:Subcellular Fractions / Q000378:metabolism*
D011059:Polonium