Synthesis, biodistribution, and estrogen receptor scintigraphy of indium-111-diethylenetriaminepentaacetic acid-tamoxifen analogue

J Pharm Sci. 1996 Jun;85(6):553-9. doi: 10.1021/js960049w.

Abstract

This study was aimed at developing a hydrophilic diethylenetriaminepentaacetic acid-tamoxifen (DTPA-Tam) analogue for use in imaging estrogen receptor positive (ER+) lesions. In rat uterine cytosol, the IC50 of DTPA-Tam conjugate was 1 microM and of tamoxifen, 2 microM. Biodistribution, autoradiography, and radionuclide imaging of 111In-DTPA-Tam in breast-tumor-bearing rats showed that tumor-to-tissue ratios increased steadily between 30 min and 48 h. The in vivo response of MCF-7 breast cancer xenografts to tamoxifen and DTPA-Tam in nude mice demonstrated that DTPA-Tam could reduce tumor growth rate. These results indicate that DTPA-Tam, a new hydrophilic ER+ ligand, might be useful in diagnosing ER+ lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / ultrastructure
  • Estradiol / metabolism
  • Female
  • Humans
  • Indium Radioisotopes* / chemistry
  • Kinetics
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / radiotherapy
  • Mammary Neoplasms, Experimental / ultrastructure
  • Mice
  • Mice, Nude
  • Pentetic Acid / chemical synthesis*
  • Pentetic Acid / pharmacokinetics
  • Pentetic Acid / pharmacology
  • Radionuclide Imaging
  • Rats
  • Rats, Inbred F344
  • Receptors, Estrogen / analysis*
  • Receptors, Estrogen / metabolism
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacokinetics
  • Tamoxifen / pharmacology
  • Tissue Distribution
  • Tritium
  • Tumor Cells, Cultured

Substances

  • Indium Radioisotopes
  • Receptors, Estrogen
  • Tamoxifen
  • Tritium
  • Estradiol
  • Pentetic Acid