Influence of sedation and data acquisition method on tracer uptake in animal models: [123I]-2-iodo-L-phenylalanine in pentobarbital-sedated tumor-bearing athymic mice.
OBJECTIVE
To minimize movement artifacts during tracer imaging studies, the animals are generally sedated. Although many reports describe the effect of barbiturates on brain function, less is published about the general impact on the extracerebral metabolism and tracer biodistribution. This report describes the influence of pentobarbital on tumor uptake of [(123)I]-2-iodo-L-phenylalanine ([(123)I]-2I-L-PA) using dissection and nuclear imaging.


METHODS
R1M tumor-bearing athymic mice were divided into two populations: untreated and pentobarbital-treated. Each group was subjected to dynamic and static planar imaging and organ dissection after [(123)I]-2I-L-PA injection. Two-compartment blood modeling was performed. Analysis of variance (ANOVA), t test and clustered boxplot analyses were used to compare the results between the treatment groups and between the data acquisition methods.


RESULTS
Two-compartment blood modeling demonstrated that pentobarbital decreased the elimination velocity and the distribution toward the peripheral compartment. Both observations lead to higher blood pool and kidney activities after administering pentobarbital. The dependence of the differential absorption/differential uptake ratio results on the factors organ, method and treatment (3-factor ANOVA) demonstrated that all factors had a significant effect. Moreover, a significant effect for method and treatment was observed for each individual organ, and the ratio of tumor to background showed additionally an ordinal interaction between the latter two factors. Although the tumor uptake values were lower when using sedation and nuclear imaging, the tumor could still be visualized.


CONCLUSIONS
An effect of sedation treatment and data acquisition method was demonstrated for 2-iodo-phenylalanine, currently under development as tumor tracer. It is recommended that animal experiments should include quantitative investigation of sedation and the data acquisition method.
Kersemans
Veerle
V
Laboratory for Radiopharmacy, Universiteit Gent, Belgium. veerle.kersemans@utoronto.ca
De Spiegeleer
Bart
B
Mertens
John
J
Slegers
Guido
G
D000818:Animals; D016477:Artifacts; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006993:Hypnotics and Sedatives / Q000008:administration & dosage; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D007457:Iodine Radioisotopes; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity / Q000187:drug effects; D010424:Pentobarbital / Q000008:administration & dosage*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012208:Rhabdomyosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014018:Tissue Distribution / Q000187:drug effects
C496694:2-iodophenylalanine; D006993:Hypnotics and Sedatives; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D010649:Phenylalanine; D010424:Pentobarbital