Fig. 4

Results from a biodistribution study in CHL GLP-1R tumour-bearing CD1 nu/nu mice 24 h after i.v. administration of the studied exendin derivatives and the reference [¹¹¹In]In-Ex4. (A) Kidney uptake 24 h after administration of the [¹¹¹In]In-labelled compounds was significantly reduced in all Ex4 derivatives carrying an MVK cleavable linker. Highest reduction was achieved with [¹¹¹In]In-MV-MVK Ex4, which displayed a 77% lower kidney uptake compared to [¹¹¹In]In-Ex4. (B) Tumour uptake of [¹¹¹In]In-Ex4 and its derivatives 24 h after administration. No significant difference in tumour uptake was observed for the different compounds, indicating that the introduction of the cleavable linkers did not affect the in vivo affinity to the target receptor. (C) Tumour-to-kidney ratio of all [¹¹¹In]In-Ex4 derivatives. [¹¹¹In]In-MV-MVK-Ex4 displays the highest tumour-to-kidney ratio, slightly outperforming [¹¹¹In]In-MVK-Ex4 with only one cleavable sequence. All tumour-to-kidney ratios of the cleavable linker derivatives [¹¹¹In]In-MVK-Ex4, [¹¹¹In]In-MV-MVK-Ex4 and [¹¹¹In]In-MVK-MVK-Ex4 are higher than that of the reference [¹¹¹In]In-Ex4, with the difference between [¹¹¹In]In-Ex4 and [¹¹¹In]In-MV-MVK-Ex4 being statistically significant. Statistics were conducted using one-way ANOVA with Dunnett’s multiple comparison test (with *p < 0.05, **p < 0.01, ***p < 0.0005 and ****p < 0.0001)