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

Erina Vlashi, Jennifer E. Sturgis, Mini Thomas, Philip S. Low

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number5393504
JournalAdvances in Civil Engineering
Volume2021
DOIs
StatePublished - 2021

Keywords

  • folic acid
  • real time imaging
  • Targeted cancer therapy
  • tumor uptake

ASJC Scopus subject areas

  • Civil and Structural Engineering

Fingerprint

Dive into the research topics of 'Real Time, Noninvasive Imaging and Quantitation of the Accumulation of Ligand-Targeted Drugs into Receptor-Expressing Solid Tumors'. Together they form a unique fingerprint.

Cite this