Fig. 4

Comparison of dual-targeting vs. single-targeting by small-animal PET imaging after systemic NIS gene transfer in vivo. Mice bearing orthotopic HuH7 liver tumors that demonstrated obvious EGFR and cMET expression (a, b) received i.v. polyplexes for single EGFR-targeting (n = 6), single cMET-targeting (n = 4) or dual-targeting (n = 7). At 48 h after NIS gene transfer, mice were injected i.p. with 10 MBq ¹²⁴I and radioiodide biodistribution was assessed by small-animal PET imaging. PET images 1 h after iodide application showed improved distribution and uptake of iodide in tumors of mice that received polyplexes for dual-targeting in comparison to animals injected with single-targeted polyplexes (c–e). NIS-specificity was verified by pretreatment of mice that received polyplexes for dual-targeting with the NIS-specific inhibitor sodium perchlorate 30 min prior to radionuclide application (n = 2). This resulted in an almost complete inhibition of iodide uptake in the tumor and organs that physiologically express NIS (f). ROIs were quantified and higher tumoral iodide uptake over 5 h was observed in tumors of mice that received polyplexes for dual-targeting (*p ≤ 0.05). Results are reported as mean % of ID ± SEM