Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer

Amino Acids. 2010 Jun;39(1):111-20. doi: 10.1007/s00726-009-0382-0. Epub 2009 Nov 26.

Abstract

In this study, we reported the preparation and evaluation of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2 (RGD2 = E[c(RGDfK)](2)) as a potential therapeutic radiotracers for the treatment of integrin alpha(v)beta(3)-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100 degrees C and higher DOTA-conjugate concentration were needed for successful (177)Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of (177)Lu-labeled cyclic RGDfK peptides, and (177)Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin alpha(v)beta(3)-positive tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dimerization
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors
  • Integrin alphaVbeta3 / chemistry
  • Integrin alphaVbeta3 / metabolism
  • Kinetics
  • Lutetium / chemistry*
  • Lutetium / metabolism
  • Lutetium / pharmacokinetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Conformation
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / metabolism
  • Organophosphorus Compounds / pharmacokinetics
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacokinetics*
  • Radioisotopes / chemistry*
  • Radioisotopes / metabolism
  • Radioisotopes / pharmacokinetics*
  • Time Factors
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Integrin alphaVbeta3
  • Organophosphorus Compounds
  • Peptides, Cyclic
  • Radioisotopes
  • cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl)
  • Lutetium