scholarly journals A sensitive and rapid HPLC-DAD method for the determination of 3-hydroxy-1,2-dimethyl-4-pyridone and its distribution in rats

2020 ◽  
Vol 19 (4) ◽  
pp. 859-864
Author(s):  
Mengdi Chen ◽  
Xuejiao Zhang ◽  
Shuling Li ◽  
Qiongyao Zhang
Keyword(s):  
Protein Binding ◽  
Tissue Distribution ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Binding Capacity ◽  
Peak Level ◽  
Hplc Method ◽  
Protein Binding Capacity

Purpose: To establish a sensitive and rapid method for the determination of the tissue distribution of 3-hydroxy-1,2-dimethyl-4-pyridone (L1) in vivo, and its plasma protein binding capacity.Methods: This study optimized a reverse-phase HPLC method for specific and sensitive determination of L1 as well as its plasma and tissue  distributions. The optimized method was used to determine the plasma protein-binding capacity of L1 in Wistar rats.Results: A rapid, sensitive and simple HPLC-DAD method was established for studying the plasma and tissue distribution of L1. Following TI  administration, its liver concentrations peaked at 60 min and 360min, followed 360 min later with peak level in the kidney (second highest). The L1 concentration was significantly lower after 360 min than after 60 min, and values of its mean binding to plasma proteins was 5.2 % at different L1 concentrations.Conclusion: These results indicate that L1 is a drug with rapid-absorption and rapid-elimination thath is distributed widely in vivo in rats. Moreover, the drug has a weak plasma protein-binding capacity. Keywords: 3-Hydroxy-1,2-dimethyl-4-pyridone, Distribution, Alzheimer’s disease, Therapy

scholarly journals Albumin-Binding PSMA Radioligands: Impact of Minimal Structural Changes on the Tissue Distribution Profile

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2542 ◽  
Author(s):  
Luisa M. Deberle ◽  
Viviane J. Tschan ◽  
Francesca Borgna ◽  
Fan Sozzi-Guo ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Protein Binding ◽  
Tissue Distribution ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Structural Changes ◽  
Albumin Binding ◽  
Distribution Profile ◽  
Tissue Distribution Profile

The concept of using ibuprofen as an albumin-binding entity was recently demonstrated by the development of [177Lu]Lu-Ibu-PSMA-01. In the present study, we designed a novel ibuprofen-containing radioligand (Ibu-PSMA-02) with subtle structural changes regarding the linker entity in order to investigate a potential impact on the in vitro and in vivo properties. Ibu-PSMA-02 was prepared using solid-phase synthesis techniques and labeled with lutetium-177. [177Lu]Lu-Ibu-PSMA-02 was evaluated in vitro with regard to its plasma protein-binding properties, PSMA affinity and uptake into PSMA-expressing PC-3 PIP tumor cells. The tissue distribution profile of [177Lu]Lu-Ibu-PSMA-02 was assessed in tumor-bearing mice and dose estimations were performed. The in vitro characteristics of [177Lu]Lu-Ibu-PSMA-02 were similar to those previously obtained for [177Lu]Lu-Ibu-PSMA-01 with respect to plasma protein-binding, PSMA affinity and tumor cell uptake. The in vivo studies revealed, however, an unprecedentedly high uptake of [177Lu]Lu-Ibu-PSMA-02 in PC-3 PIP tumors, resulting in an increased absorbed tumor dose of 7.7 Gy/MBq as compared to 5.1 Gy/MBq calculated for [177Lu]Lu-Ibu-PSMA-01. As a consequence of the high tumor accumulation, [177Lu]Lu-Ibu-PSMA-02 showed higher tumor-to-background ratios than [177Lu]Lu-Ibu-PSMA-01. This study exemplified that smallest structural changes in the linker entity of PSMA radioligands may have a significant impact on their pharmacokinetic profiles and, thus, may be applied as a means for ligand design optimization.

scholarly journals Gallium-68-Labelled Indocyanine Green as a Potential Liver Reserve Imaging Agent

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Yuxiao Xia ◽  
Li Zhang ◽  
Yanhong Zhao ◽  
Xiangdong Liu ◽  
Liang Cai ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Water Solubility ◽  
Time Points ◽  
Binding Rate ◽  
Very High

Objective. This work evaluated the potential of 68Ga-labelledNOTA-ICG (1,4,7-triazacyclononane-1,4,7-triacetic acid indocyanine green) for liver reserve imaging. Methods. To determine the optimal conditions for generating 68Ga-NOTA-ICG, various reaction parameters were implemented. Quality control analysis was performed using different chromatography techniques. The in vitro and in vivo stability was also measured at specific time points. The radioactivity ratio between n-octanol and water was determined to evaluate the water solubility of 68Ga-NOTA-ICG. The plasma-protein binding rate of the labelled compound was determined by the methanol method. The biodistribution and imaging findings were evaluated in normal animals at different time points after injection. A preliminary imaging evaluation was performed using an animal model of hepatic ischaemia-reperfusion injury, which was confirmed by pathology. Results. 68Ga-NOTA-ICG was prepared with very high radiochemical purity (>98%) by reacting at 90°C for 10 min at pH = 3.5∼4.0, with excellent stability in vivo and in vitro (>95% 3 h postpreparation). The in vitro plasma-protein binding rate of 68Ga-NOTA-ICG was 13.01 ± 0.7%, and it showed strong water solubility log P=−2.01±0.04. We found that in addition to excretion through the biliary tract and intestines, 68Ga-NOTA-ICG can be excreted through the urinary tract. The image quality of 68Ga-NOTA-ICG was very high; imaging agent retained in the area of liver injury could clearly be observed. Conclusion. This is the first report on a 68Ga-labelled NOTA-ICG fragment for liver reserve function studies. This complex has promise as a candidate agent for liver reserve imaging.

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