title: Reduction of renal uptake of 111In-DOTA-labeled and A700-labeled RAFT-RGD during integrin αvβ3 targeting using single photon emission computed tomography and optical imaging.
abstract: Integrin α(v)β(3) expression is upregulated during tumor growth and invasion in newly formed endothelial cells in tumor neovasculature and in some tumor cells. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin α(v)β(3) in vitro and in vivo. When labeled with indium-111, the RAFT-RGD is partially reabsorbed and trapped in the kidneys, limiting its use for further internal targeted radiotherapy and imaging investigations. We studied the effect of Gelofusine on RAFT-RGD renal retention in tumor-bearing mice. Mice were imaged using single photon emission computed tomography and optical imaging 1 and 24 h following tracer injection. Distribution of RAFT-RGD was further investigated by tissue removal and direct counting of the tracer. Kidney sections were analyzed by confocal microscopy. Gelofusine significantly induced a >50% reduction of the renal reabsorption of (111)In-DOTA-RAFT-RGD and A700-RAFT-RGD, without affecting tumor uptake. Injection of Gelofusine significantly reduced the renal retention of labeled RAFT-RGD, while increasing the tumor over healthy tissue ratio. These results will lead to the development of future therapeutic approaches.
authors.affiliation: INSERM U877, Radiopharmaceutiques Biocliniques, Grenoble, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Briat
authors.forename: Christiane H F
authors.initials: CH
authors.lastname: Wenk
authors.forename: Mitra
authors.initials: M
authors.lastname: Ahmadi
authors.forename: Michael
authors.initials: M
authors.lastname: Claron
authors.forename: Didier
authors.initials: D
authors.lastname: Boturyn
authors.forename: Véronique
authors.initials: V
authors.lastname: Josserand
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Daniel
authors.initials: D
authors.lastname: Fagret
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.forename: Catherine
authors.initials: C
authors.lastname: Ghezzi
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vuillez
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005456:Fluorescent Dyes; D057809:HEK293 Cells; D006801:Humans; D007204:Indium / Q000378:metabolism; D007205:Indium Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D064847:Multimodal Imaging; D009942:Organometallic Compounds / Q000378:metabolism / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000378:metabolism / Q000493:pharmacokinetics*; D011097:Polygeline / Q000494:pharmacology*; D049268:Positron-Emission Tomography; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: C532506:111In-DOTA-cyclo(arginyl-glycyl-aspartyl-phenylalanyl-lysyl); D005456:Fluorescent Dyes; D007205:Indium Radioisotopes; D039302:Integrin alphaVbeta3; D009942:Organometallic Compounds; D010456:Peptides, Cyclic; C574552:RAFT-RGD; D007204:Indium; D011097:Polygeline