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- W2061574274 abstract "Targeted therapies are emerging as a preferred strategy for treatment of cancer and other diseases. To evaluate the effect of high affinity receptors on the rate and extent of tumor penetration of receptor-targeted drugs, we have characterized the kinetics of folate−rhodamine uptake by folate receptor (FR)-expressing tumors in live mice. Folate−rhodamine was selected to model receptor-targeted drugs, because (i) it has high affinity (Kd = 10−9 M) for FR-rich tumors, (ii) its uptake can be monitored in vivo by multiphoton microscopy, and (iii) five folate-targeted drugs of similar size are currently undergoing clinical trials. We demonstrate that (1) folate−rhodamine saturates tumor FR in <5 min, <30 min, and <100 min following intravenous, paraorbital, and intraperitoneal injection, respectively; (2) complete clearance of folate−rhodamine from receptor-negative tissues requires ≥50 min, and (3) a “binding site barrier” may retard, but does not prevent, penetration of the ligand-targeted drug. We conclude that low molecular weight ligand-targeted drugs have appropriate pharmacokinetic properties for tumor-selective delivery." @default.
- W2061574274 created "2016-06-24" @default.
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- W2061574274 date "2009-10-14" @default.
- W2061574274 modified "2023-09-30" @default.
- W2061574274 title "Real Time, Noninvasive Imaging and Quantitation of the Accumulation of Ligand-Targeted Drugs into Receptor-Expressing Solid Tumors" @default.
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- W2061574274 doi "https://doi.org/10.1021/mp900158d" @default.
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