Real Time, Noninvasive Imaging and Quantitation of the Accumulation of Ligand-Targeted Drugs into Receptor-Expressing Solid Tumors

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 (K d = 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