%0 Journal Article %A Steve Lenhard %A Allen McAlexander %A Anthony Virtue %A William Fieles %A Tina Skedzielewski %A Mary Rambo %A Han Trinh %A Shih-Hsun Cheng %A Hyundae Hong %A Albert Isidro-Llobet %A Alan Nadin %A Robert Geske %A Jean-Louis Klein %A Dennis Lee %A Beat M Jucker %A Erding Hu %T In Vivo Imaging of Small Molecular Weight Peptides for Targeted Renal Drug Delivery: A Study in Normal and Polycystic Kidney Diseased Mice %D 2019 %R 10.1124/jpet.119.257022 %J Journal of Pharmacology and Experimental Therapeutics %P jpet.119.257022 %X Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a leading monogenetic cause of end stage renal disease (ESRD) with limited therapeutic repertoire. A targeted drug delivery strategy that directs a small molecule to renal niches around cysts could increase safety margins of agents that slow the progression of ADPKD but are poorly tolerated due to extra-renal toxicity. Herein, we determined whether previously characterized lysine- and glutamic acid-based, megalin-binding peptides can achieve renal specific localization in the Juvenile Cystic Kidney (JCK) mouse model of polycystic kidney disease and if the distribution is altered compared to control mice. We performed in vivo optical and MRI imaging studies using peptides conjugated to the VivoTag 680 dye and demonstrated that megalin-interacting peptides distributed almost exclusively to the kidney cortex in both normal and JCK mice. Confocal analysis demonstrated that the peptide-dye conjugate distribution overlapped with megalin-positive renal proximal tubules. However, in the JCK mouse, the epithelium of renal cysts did not retain expression of the proximal tubule markers aquaporin 1 and megalin, and therefore these cysts did not retain peptide-dye conjugates. Furthermore, human kidney tumor tissues were evaluated by immunohistochemistry and revealed significant megalin expression in tissues from renal cell carcinoma patients, raising the possibility that these tumors could be treated using this drug delivery strategy. Taken together, our data suggest that linking a small molecule drug to these carrier peptides could represent a promising opportunity to develop a new platform for renal enrichment and targeting in the treatment of ADPKD and certain renal carcinomas. %U https://jpet.aspetjournals.org/content/jpet/early/2019/04/02/jpet.119.257022.full.pdf