PT  - JOURNAL ARTICLE
AU  - Liu, Jun
AU  - Hajibeigi, Asghar
AU  - Lin, Mai
AU  - Sun, Xiankai
AU  - Oz, Orhan K.
TI  - Genetic background differences in murine hepatic retention of 64Cu-ATSM is associated with differential expression of multidrug resistance protein 3
DP  - 2009 May 01
TA  - Journal of Nuclear Medicine
PG  - 273--273
VI  - 50
IP  - supplement 2
4099  - http://jnm.snmjournals.org/content/50/supplement_2/273.short
4100  - http://jnm.snmjournals.org/content/50/supplement_2/273.full
SO  - J Nucl Med2009 May 01; 50
AB  - 273 Objectives 64Cu-ATSM [copper -diacetyl-bis(N4-methylthiosemicarbazone)] is a PET hypoxia imaging tracer. The reductive retention of Cu-ATSM is determined by NADH-cytochrome b5 reductase, NADPH-cytochrome P450 reductase. Retention is also influenced by the multidrug resistance protein 1 (MDR1). Genetic background may influence the expression and activity of these enzymes and protein and thus influence retention. To test this hypothesis, biodistribution of 64Cu-ATSM was performed in two different strains of mice and expression and/or activity of the proteins was determined. Methods B6 and 129 mice were used for the biodistribution (n= 5 per group, 0.37MBq per mouse, 1 h uptake) and PET/CT imaging (1 h dynamic) to examine the retention difference of 64Cu-ATSM between the two strains. Real time PCR and western blot were used to determine the mRNA and protein levels, respectively. Enzyme activity of NADH-cytochrome b5 reductase and NADPH-cytochrome P450 reductase was also measured using commercially available kits. Results Higher radiotracer activity was seen in liver of 129 mice than in B6 mice (p<0.05). On the other hand, cytochrome P450 reductase expression and activity was much higher in the liver of B6 mice. Cytochrome b5 reductase activity was not different between groups. Multidrug resistance Related Protein 3 (MPR3) protein level was much lower in 129 mice (p<0.05) but there was no difference in MDR1 expression. Conclusions Hepatic retention of 64Cu-ATSM varies with the genetic background in mice. Differences in MRP3 expression may in part account for the difference in retention. The study raises the question of whether 64Cu-ATSM is a substrate for MRP3.