Fluorescence Imaging Using Enzyme-Activatable Probes for Detecting Diabetic Kidney Disease and Glomerular Diseases

Abstract

A clear identification of the etiology of glomerular disease is essential in patients with diabetes. Renal biopsy is the gold standard for assessing the underlying nephrotic pathology; however, it has the risk for potential complications. Here, we aimed to investigate the feasibility of urinary fluorescence imaging using an enzyme-activatable probe for differentiating diabetic kidney disease and the other glomerular diseases. Hydroxymethyl rhodamine green (HMRG)-based fluorescent probes targeting gamma-glutamyl transpeptidase (GGT) and dipeptidyl-peptidase (DPP) were used. Urinary fluorescence was compared between groups which were classified by their histopathological diagnoses (diabetic kidney disease, glomerulonephritis, and nephrosclerosis) as obtained by ultrasound-guided renal biopsy. Urinary fluorescence was significantly stronger in patients with diabetic kidney disease compared to those with glomerulonephritis/nephrosclerosis after DPP-HMRG, whereas it was stronger in patients with nephrosclerosis than in patients with glomerulonephritis after GGT-HMRG. Subgroup analyses of the fluorescence performed for patients with diabetes showed consistent results. Urinary fluorescence imaging using enzyme-activatable fluorescence probes thus represents a potential noninvasive assessment technique for kidney diseases in patients with diabetes.

Advances and Perspectives of Responsive Probes for Measuring γ-Glutamyl Transpeptidase

“…For other normal tissues, fluorescence signal was not observed due to the limited expression of GGT, which created a high signal-to-noise (S/N) ratio for cancer diagnosis. Following research included spraying γGlu-HMRG for rapid diagnosis of metastatic lymph nodes (mLNs) of colorectal cancer, for visualization of the leakage of pancreatic juice after digestive surgery, and for colorectal tumor imaging, intravenous administration of γGlu-HMRG for deeply located tumors, like lung tumor diagnosis, , and urinalysis of GGT for diagnosis of diabetic kidney and glomerular diseases …”

A Fluorescent Probe for the Detection of γ‐Glutamyl Transpeptidase Activity and its Application in Garlic

“…The development of GGT fluorescent probes mainly focuses on modifying fluorescent groups. Currently, the reported fluorescent groups include rhodamine, [27] coumarin, [28] diacyclomethyl, [29] xanthene, [30] boron dipyrromethene, [31] naphthalimide, [32] cyanine, [33] dihydrofuran, [34] pyronin, [35] isophorone, [36] benzothiazole, [37] quinazoline, [38] and tetrafluoroorephethalonitrile. [39] Although many GGT fluorescent probes have been developed for the detection of biological diseases.…”