JOURNAL OF MEDICINAL CHEMISTRY
·
2024
·
IF 6.8
Zuojie Li,Xiaojiang Duan,Peiwen Han,Guangxing Yin,Yuhao Jiang,Qing Ruan,Junbo Zhang
The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment of prostate cancer (PCa). This study aimed to improve the absolute tumor uptake and tumor-to-background ratios (TBRs) of this novel PSMA tracer by increasing the number of pharmacophores, Glu-urea-Lys (EuK), that specifically bind to PSMA. We successfully synthesized four radioligands and prepared a total of 12 stable radiotracers by coordinating 99mTc with various coligands. [99mTc]Tc-EUKD-EDDA showed the best pharmacokinetic properties both in vitro and in vivo. It effectively increased the absolute uptake in tumors and resulted in good tumor retention. Rapid clearance in nontarget organs resulted in high TBRs. High-contrast SPECT/CT images were obtained within 2–6 h after injection, suggesting that [99mTc]Tc-EUKD-EDDA has great application potential in time-lapse imaging of PCa, which is important for improving the diagnostic accuracy of PCa in clinical practice.
研究领域:
医学影像学
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核医学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Haiyan Hong,Zhihao Zha,Ruiyue Zhao,Yang Luo,Wenbin Jin,Linlin Li,Ran Wang,Li Yan,Hui Wang,Karl Ploessl,Jinping Qiao,Lin Zhu,Hank F. Kung
Fibroblast activation protein (FAP) is selectively expressed in tumors and highly important for maintaining the microenvironment in malignant tumors. Radioisotope-labeled FAP inhibitors (FAPIs) were proven to be useful for diagnosis and radionuclide therapy of cancer and are under active clinical investigations. Ga-HBED complex displays a higher in vivo stability constant (log KGaL: 38.5), compared to that of Ga-DOTA (log KGaL: 21.3). Such advantage in stability constant suggests that it may be useful for development of alternative FAPI imaging agents. In this study, previously reported [68Ga]Ga-DOTA-FAPI-02 and -04 were converted to the corresponding [68Ga]Ga-HBED-CC-FAPI-02 and -04 derivatives ([68Ga]Ga-4, [68Ga]Ga-5, [68Ga]Ga-6, and [68Ga]Ga-7). It was found that substituting the DOTA chelating group with HBED-CC led to several unique and desirable tumor-targeting properties: (1) robust, fast, and high yield labeling─readily adaptable to a kit formulation; (2) high stabilities in vitro; (3) excellent FAP binding affinities (IC50 ranging between 4 and 7 nM) and improved cell uptake and retention (in HT1080 (FAP+) cells); and (4) excellent selective in vivo tumor uptake in nude mice bearing U87MG tumor. It appeared that Ga(III) chelation with HBED-CC improved the in vivo kinetics favoring higher tumor uptake and retention compared to the corresponding Ga-DOTA complex. Out of the four tested ligands the new [68Ga]Ga-HBED-CC-FAPI dimer, [68Ga]Ga-6, displayed the best tumor localization properties, and further studies are warranted to demonstrate that it is an alternative FAP imaging agent for cancer patients.
研究领域:
医学影像学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2025
·
IF 2.2
Yaxin Qin,Qi Dai,Zhicheng Zhang,Xiaoyan Sun,Ruolin Jiang,Xiaoyan Bao,Linjie Wu,Xin Tan,Xufang Ying,Zhiqing Ben,Qichun Wei,Min Han
Objective Boron Neutron Capture Therapy (BNCT) is a novel precision radiotherapy. The key to BNCT application lies in the effective targeting and retention of the boron-10 (10B) carrier. Among the various compounds studied in clinical settings, 4-boronophenylalanine (BPA) become the most prevalent one currently. However, challenges such as inadequate solubility and restricted tumor accumulation have affected the clinical efficacy of treatment with BPA. Therefore, there is an urgent need to prepare formulations with higher tumor uptake efficiency and increased intratumoral accumulation.Methods polyethylene glycol 400 and BPA were added to methanol and stirred until completely dissolved. The solution was then evaporated to remove methanol, yielding a pale-yellow clear liquid of the PEG400-BPA complex. This complex was then used for in vitro and in vivo experiments, and it was evaluated for inhibition effects after BNCT irradiation in GL261 cells.Results Compared to the clinically used fructose-BPA, PEG400-BPA increased the boron uptake in tumor cells nearly twice and exhibited a better tumor-to-normal tissue ratio (T/N) in the in vivo studies. Due to the BNCT efficacy with PEG400-BPA through in vitro experiments, the PEG400-BPA group also had showed significant cell-killing effects.Conclusion We discovered that PEG400 can form a complex with BPA, significantly improving its water solubility. It provides a simple, long-term stable, easily convertible, and injectable formulation method for the delivery of BPA in BNCT treatment. It also offers new insights for BPA solubilization and formulation as well as compound forms of administration of boron drugs on the delivery of boron drugs in BNCT.
研究领域:
肿瘤学
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药剂学
·
放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY
·
2019
·Vol. 319
·期 3
·1119-1125
·
IF 1.186
Wang Yunhan,Song Hu,Wang Guanquan,Yang Xia,Wang Jing,Wei Hongyuan
In this study, we successfully synthesized polyethylene glycol (PEG) and folic acid (FA) co-functionalized graphene quantum dots (GQDs) to improve the biocompatibility and tumor-targeting ability of GQDs simultaneously, and labeled GQDs–PEG–FA with 131 I for biological behavior evaluation. The in vitro properties, biodistribution and SPECT imaging of 131 I-GQDs–PEG–FA were investigated. The uptake of 131 I-GQDs–PEG–FA at tumor sites can be clearly examined via SPECT imaging, which can ascribe to enhanced permeability and retention effect and active targeting effect of FA to folate receptors. The results indicate that 131 I-GQDs–PEG–FA can be used as a radioactive probe for detection of tumor cells overexpressing folate receptor.
研究领域:
放射学
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核医学
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分子影像
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生物材料
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癌症研究
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）