title: A porphyrin-PEG polymer with rapid renal clearance.
abstract: Tetracarboxylic porphyrins and polyethylene glycol (PEG) diamines were crosslinked in conditions that gave rise to a water-soluble porphyrin polyamide. Using PEG linkers 2 kDa or larger prevented fluorescence self-quenching. This networked porphyrin mesh was retained during dialysis with membranes with a 100 kDa pore size, yet passed through the membrane when centrifugal filtration was applied. Following intravenous administration, the porphyrin mesh, but not the free porphyrin, was rapidly cleared via renal excretion. The process could be monitored by fluorescence analysis of collected urine, with minimal background due to the large Stokes shift of the porphyrin (230 nm separating excitation and emission peaks). In a rhabdomyolysis mouse model of renal failure, porphyrin mesh urinary clearance was significantly impaired. This led to slower accumulation in the bladder, which could be visualized non-invasively via fluorescence imaging. Without further modification, the porphyrin mesh was chelated with (64)Cu for dynamic whole body positron emission tomography imaging of renal clearance. Together, these data show that small porphyrin-PEG polymers can serve as effective multimodal markers of renal function.
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Radiology and Medical Physics, University of Wisconsin, Madison, WI, USA.
authors.forename: Reinier
authors.initials: R
authors.lastname: Hernandez
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Jumin
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Haotian
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Wentao
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Radiology and Medical Physics, University of Wisconsin, Madison, WI, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Radiology and Medical Physics, University of Wisconsin, Madison, WI, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Graves
authors.affiliation: Department of Radiology and Medical Physics, University of Wisconsin, Madison, WI, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nickles
authors.affiliation: Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Radiology and Medical Physics, University of Wisconsin, Madison, WI, USA.
authors.forename: Weibo
authors.initials: W
authors.lastname: Cai
authors.affiliation: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA; Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Buffalo, NY, USA. Electronic address: jflovell@buffalo.edu.
authors.forename: Jonathan F
authors.initials: JF
authors.lastname: Lovell
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007668:Kidney / Q000503:physiopathology*; D051379:Mice; D008813:Mice, Inbred ICR; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D051437:Renal Insufficiency / Q000000981:diagnostic imaging / Q000503:physiopathology
chemical_list: D011166:Porphyrins; D011092:Polyethylene Glycols
keywords: Acute renal failure; Fluorescence imaging; Polyamide; Porphyrin; Positron emission tomography; Renal clearance