体内分布
多塔
化学
体外
前列腺癌
正电子发射断层摄影术
谷氨酸羧肽酶Ⅱ
药代动力学
显像剂
螯合作用
癌症研究
体内
核医学
分子生物学
药理学
医学
癌症
生物化学
内科学
生物
生物技术
有机化学
作者
Inki Lee,Min Hwan Kim,Kyongkyu Lee,Keumrok Oh,Hyunwoo Lim,Junmo Ahn,Yong Jin Lee,Gi Jeong Cheon,Dae Hwan Yoon,Sang Moo Lim
出处
期刊:Diagnostics
[MDPI AG]
日期:2023-08-11
卷期号:13 (16): 2649-2649
标识
DOI:10.3390/diagnostics13162649
摘要
Background: This study compared the effects of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) as 64Cu-chelating agents in newly developed prostate-specific membrane antigen (PSMA) target compounds, 64Cu-cudotadipep and 64Cu-cunotadipep, on pharmacokinetics. Methods: The in vitro stability of the chelators was evaluated using human and mouse serum. In vitro PSMA-binding affinity and cell uptake were compared using human 22Rv1 cells. To evaluate specific PSMA-expressing tumor-targeting efficiency, micro-positron emission tomography (mcroPET)/computed tomography (CT) and biodistribution analysis were performed using PSMA+ PC3-PIP and PSMA− PC3-flu tumor xenografts. Results: The serum stability of DOTA- or NOTA-conjugated 64Cu-cudotadipep and 64Cu-cunotadipep was >97%. The Ki value of the NOTA derivative, cunotadipep, in the in vitro affinity binding analysis was higher (2.17 ± 0.25 nM) than that of the DOTA derivative, cudotadipep (6.75 ± 0.42 nM). The cunotadipep exhibited a higher cellular uptake (6.02 ± 0.05%/1 × 106 cells) compared with the cudotadipep (2.93 ± 0.06%/1 × 106 cells). In the biodistribution analysis and microPET/CT imaging, the 64Cu-labeled NOTA derivative, 64Cu-cunotadipep, demonstrated a greater tumor uptake and lower liver uptake than the DOTA derivative. Conclusions: This study indicates that the PSMA-targeted 64Cu-cunotadipep can be applied in clinical practice owing to its high diagnostic power for prostate cancer.
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