Tricarbocyanine cholesteryl laurates labeled LDL: new near infrared fluorescent probes (NIRFs) for monitoring tumors and gene therapy of familial hypercholesterolemia

Bioorg Med Chem Lett. 2002 Jun 3;12(11):1485-8. doi: 10.1016/s0960-894x(02)00193-2.

Abstract

For monitoring low-density lipoprotein receptors (LDLr) in tumors and in livers of patients with familial hypercholesterolemia (FH) treated with gene therapy, a series of tricarbocyanine cholesteryl laurates were synthesized with the cholesteryl laurate moiety serving as the lipid-chelating anchor for low-density lipoprotein (LDL). One of these conjugates, TCL17, was successfully used to label LDL to give a new NIRF, TCL17-LDL. Ex vivo biological studies on an LDLr overexpressing tumor model, human hepatoblastoma G(2) (HepG(2)), confirmed that this NIRF were internalized selectively by the tumor and detected with high sensitivity by a low-temperature 3-D redox scanner.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carbocyanines / chemical synthesis
  • Carbocyanines / chemistry
  • Carbocyanines / pharmacokinetics
  • Cholesterol Esters / chemistry
  • Cholesterol Esters / metabolism*
  • Cholesterol Esters / pharmacokinetics
  • Cholesterol, LDL / chemical synthesis
  • Cholesterol, LDL / chemistry
  • Cholesterol, LDL / metabolism*
  • Cholesterol, LDL / pharmacokinetics
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / metabolism*
  • Fluorescent Dyes / pharmacokinetics
  • Genetic Therapy
  • Hepatoblastoma / drug therapy
  • Hepatoblastoma / metabolism*
  • Humans
  • Hyperlipoproteinemia Type II / metabolism*
  • Hyperlipoproteinemia Type II / therapy
  • Imaging, Three-Dimensional
  • Laurates / chemical synthesis
  • Laurates / chemistry
  • Laurates / metabolism*
  • Laurates / pharmacokinetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / therapy
  • Mice
  • Receptors, LDL / metabolism*
  • Spectroscopy, Near-Infrared

Substances

  • Carbocyanines
  • Cholesterol Esters
  • Cholesterol, LDL
  • Fluorescent Dyes
  • Laurates
  • Receptors, LDL