733009-36-4Relevant academic research and scientific papers
Design of Turn-On Near-Infrared Fluorescent Probes for Highly Sensitive and Selective Monitoring of Biopolymers
Ducharme, Gerard T.,LaCasse, Zane,Nesterov, Evgueni E.,Nesterova, Irina V.,Sheth, Tanya
, p. 8440 - 8444 (2020/03/24)
Simple, sensitive, and selective detection of specific biopolymers is critical in a broad range of biomedical and technological areas. We present a design of turn-on near-infrared (NIR) fluorescent probes with intrinsically high signal-to-background ratio
High-affinity epidermal growth factor receptor (EGFR) irreversible inhibitors with diminished chemical reactivities as positron emission tomography (PET)-imaging agent candidates of EGFR overexpressing tumors
Mishani, Eyal,Abourbeh, Galith,Jacobson, Orit,Dissoki, Samar,Ben Daniel, Revital,Rozen, Yulia,Shaul, Mazal,Levitzki, Alexander
, p. 5337 - 5348 (2007/10/03)
Previous studies with the anilinoquinazoline epidermal growth factor receptor (EGFR) irreversible inhibitor [11C]-ML03 demonstrated a rapid metabolism of the tracer, which led to its low in vivo accumulation in EGFR overexpressing tumors. To enhance tumor uptake, the chemical structure of the compound was modified, and four new groups of EGFR inhibitors with a wide range of chemical reactivities were synthesized. Chemical reactivity assay of the compounds, performed with reduced glutathione (GSH), revealed that the group C (4-(dimethylamino)-but-2-enoic amide) derivative was the least chemically reactive against the nucleophilic attack of GSH. Nonetheless, it demonstrated a high inhibitory potency and bound irreversibly to the EGFR. Consequently, the blood stability of the group C compound (5a, ML04) labeled with 11C was studied. In a time frame of 60 min, no radioactive metabolites were detected in blood. The stability of [11C]-5a, as indicated both from in vitro blood-stability assays and injection into nude rats, was significantly higher as compared to [11C]-ML03. Since group C presented a greater promise for tumor accumulation, it represents, to date, the most suitable candidate for radiolabeling with long-lived positron emission tomography (PET) radioisotopes.
Novel iodine-124 labeled EGFR inhibitors as potential PET agents for molecular imaging in cancer
Shaul, Mazal,Abourbeh, Galith,Jacobson, Orit,Rozen, Yulia,Laky, Desideriu,Levitzki, Alexander,Mishani, Eyal
, p. 3421 - 3429 (2007/10/03)
The in vivo results with our previously reported irreversible labeled inhibitor [11C]-ML03 suggested that more chemically stable inhibitors, labeled with a longer-lived radioisotope, could be better candidates for molecular imaging of epidermal growth factor receptor (EGFR) positive tumors. On the basis of this hypothesis we synthesized three new irreversible tyrosine kinase (TK) inhibitors with various chemical reactivities. The three new inhibitors were successfully labeled on the anilino moiety with [ 124I], starting with the 6-amino-4-[(3-tributylstannylphenyl)amino]- quinazoline (9) precursor. The cell-free results, obtained with these new irreversible inhibitors, indicated that compounds 5 (α-chloro-acetamide derivative) and 6 (4-dimethylamino-but-2-enoic amide derivative) possessed high potencies toward the EGFR with an irreversible inhibition effect. Compound 4 (α-methoxy-acetamide derivative) was found to be less potent, with only a partially irreversible effect. The high potency of compounds 5 and 6 toward the EGFR establishes their potential as PET agents for molecular imaging of EGFR positive tumors. Their prospect as PET biomarkers is further being investigated.
