Fluorescently Labeled Cyclodextrin Derivatives as Exogenous Markers for Real-Time Transcutaneous Measurement of Renal Function.
Evaluation of renal function is crucial for a number of clinical situations. Here, we reported a novel exogenous fluorescent marker (FITC-HPβCD) to real-time assess renal function by using a transcutaneous fluorescent detection technique. FITC-HPβCD was designed based on the principle of renal clearance of designed drugs. It displays favorable fluorescent properties, high hydrophilicity, low plasma protein binding, and high stability in porcine liver esterase as well as in plasma and nontoxicity. More importantly, FITC-HPβCD can be efficiently and rapidly filtered by glomerulus and completely excreted into urine without proximal tubular reabsorption or secretion in rat models. Additionally, the marker was well-tolerated, with nearly 100% urinary recovery of the given doses, and no metabolism were found. Relying on this novel kidney function marker and transcutaneous devices, we demonstrate a rapid, robust, and convenient approach for real-time assessing renal function without the need of time-consuming blood and urine sample preparation. Our work provides a promising tool for noninvasive real-time monitoring of renal function in vivo.
Medical Research Center, Medical Faculty Mannheim, University of Heidelberg , 68167 Mannheim, Germany.
Jiaguo
J
Huang
Medical Research Center, Medical Faculty Mannheim, University of Heidelberg , 68167 Mannheim, Germany.
Stefanie
S
Weinfurter
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , 3584 CG Utrecht, The Netherlands.
Pedro Caetano
PC
Pinto
Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim, University of Heidelberg , 68167 Mannheim, Germany.
Marc
M
Pretze
Medical Research Center, Medical Faculty Mannheim, University of Heidelberg , 68167 Mannheim, Germany.
Bettina
B
Kränzlin
Medical Research Center, Medical Faculty Mannheim, University of Heidelberg , 68167 Mannheim, Germany.
Johannes
J
Pill
Cyanagen S.r.l. , 40138 Bologna, Italy.
Rodeghiero
R
Federica
Cyanagen S.r.l. , 40138 Bologna, Italy.
Rossana
R
Perciaccante
Cyanagen S.r.l. , 40138 Bologna, Italy.
Leopoldo Della
LD
Ciana
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University , 3584 CG Utrecht, The Netherlands.
Rosalinde
R
Masereeuw
Medical Research Center, Medical Faculty Mannheim, University of Heidelberg , 68167 Mannheim, Germany.
Norbert
N
Gretz
D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism* / Q000652:urine*; D001798:Blood Proteins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003505:Cyclodextrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000652:urine; D004355:Drug Stability; D004950:Esterases / Q000378:metabolism; D019793:Fluorescein / Q000737:chemistry; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007677:Kidney Function Tests / Q000295:instrumentation / Q000379:methods*; D055095:Optics and Photonics / Q000379:methods; D017207:Rats, Sprague-Dawley; D013552:Swine
D015415:Biomarkers; D001798:Blood Proteins; D003505:Cyclodextrins; D005456:Fluorescent Dyes; D004950:Esterases; D016650:Fluorescein-5-isothiocyanate; D019793:Fluorescein