Peptide-based MRI contrast agent and near-infrared fluorescent probe for intratumoral legumain detection.

Recent studies suggest that intratumoral legumain promotes tumorigenesis. To monitor legumain activity in tumors, we developed a new MRI contrast agent ([Gd-NBCB-TTDA-Leg(L)]) and a NIR fluorescence probe (CyTE777-Leg(L)-CyTE807). The MRI contrast agent was prepared by introduction of cyclobutyl and benzyl group residues to TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triaza-dodecanedioic acid), followed by the attachment of a legumain-specific substrate peptide (Leg(L)). The NIR fluorescence probe was designed by conjugating two NIR fluorochromes (CyTE777 and CyTE807) with Leg(L). Peptide cleavage of the MRI contrast agent by legumain can increase its hydrophobicity and promote rotational correlation time (τ(R)). Peptide cleavage of the NIR probes by the legumain relieves the self quench of the probe. Peptide cleavage of the MRI contrast agent and the NIR fluorescence probe by legumain were confirmed by T1 relaxometric studies and by fluorescence studies, respectively. In vivo MR images showed that [Gd-NBCB-TTDA-Leg(L)] attained 55.3 fold (254.2% versus 4.6%, at 2.0 h post-injection) higher imaging enhancement, as compared with control contrast agent bearing a noncleaveable peptide ([Gd-NBCB-TTDA-Leg(D)], in the CT-26 (legumain(+)) tumors. Similarly, optical imaging probe CyTE777-Leg(L)-CyTE807 attained 15.2 fold (3.34 × 10(9) photons/min versus 0.22 × 10(9) photons/min, at 24.0 h post-injection) higher imaging enhancement in the CT-26 (legumain(+)) tumors, compared to a NIR control probe (CyTE777-Leg(D)-CyTE807). These data indicate that the [Gd-NBCB-TTDA-Leg(L)] and the CyTE777-Leg(L)-CyTE807 probes may be promising tools to image the legumain-expressing cancers for diagnoses and targeted treatments.

Study on hyperuricemia in HBV-associated glomerulonephritis.

OBJECTIVES: To determine the prevalence and risk factors for hyperuricemia in hepatitis B virus-associated glomerulonephritis (HBV-GN). METHODS: Univariate and multivariate logistic regression analysis was applied to decide the risk factors of hyperuricemia in HBV-GN, and clinical and pathologic data were compared between HBV-GN patients with hyperuricemia and those with normal serum uric acid. RESULTS: Among our 227 HBV-GN cases, 31.3% of the patients had hyperuricemia at the time of renal biopsy. Univariate analysis showed that the level of serum creatinine and the severity of glomerular and tubular interstitial injury were significantly related to hyperuricemia. Multivariate logistic regression analysis identified the levels of serum creatinine and tubular interstitial injury as independent factors for hyperuricemia. The incidence of hypertension and lower estimated glomerular filtration rate was significantly higher in hyperuricemic patients with HBV-GN than in normouricemic patients. There were also fewer membranous nephropathy, more proliferative sclerosing glomerulonephritis, and more tubular interstitial injury in hyperuricemic patients with HBV-GN. CONCLUSIONS: Our study results suggest that hyperuricemia is common in HBV-GN, which may facilitate the progression of HBV-GN and renal tubular interstitial injury as well as the development of hypertension.