Targeted functional imaging of estrogen receptors with 99mTc-GAP-EDL

Eur J Nucl Med Mol Imaging. 2007 Mar;34(3):354-62. doi: 10.1007/s00259-006-0191-6. Epub 2006 Sep 22.


Purpose: To evaluate the feasibility of using (99m)Tc-glutamate peptide-estradiol in functional imaging of estrogen receptor-positive [ER(+)] diseases.

Methods: 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. Cellular uptake studies of (99m)Tc-GAP-EDL were conducted in ER(+) cell lines (MCF-7, 13762 and T47D). To demonstrate whether GAP-EDL increases MAP kinase activation, Western blot analysis of GAP-EDL was performed in 13762 cells. Biodistribution was conducted in nine rats with 13762 breast tumors at 0.5-4 h. Each rat was administered (99m)Tc-GAP-EDL. Two animal models (rats and rabbits) were created to ascertain whether tumor uptake of (99m)Tc-GAP-EDL was via an ER-mediated process. In the tumor model, breast tumor-bearing rats were pretreated with diethylstilbestrol (DES) 1 h prior to receiving (99m)Tc-GAP-EDL. In the endometriosis model, part of the rabbit uterine tissue was dissected and grafted to the peritoneal wall. The rabbit was administered with (99m)Tc-GAP-EDL.

Results: There was a 10-40% reduction in uptake of (99m)Tc-GAP-EDL in cells treated with DES or tamoxifen compared with untreated cells. Western blot analysis showed an ERK1/2 phosphorylation process with GAP-EDL. Biodistribution studies showed that tumor uptake and tumor-to-muscle count density ratio in (99m)Tc-GAP-EDL groups were significantly higher than those in (99m)Tc-GAP groups at 4 h. Among (99m)Tc-GAP-EDL groups, region of interest analysis of images showed that tumor-to muscle ratios were decreased in blocking groups. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL.

Conclusion: Cellular or tumor uptake of (99m)Tc-GAP-EDL occurs via an ER-mediated process. (99m)Tc-GAP-EDL is a useful agent for imaging functional ER(+) disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / diagnostic imaging*
  • Breast Neoplasms / metabolism*
  • Drug Delivery Systems / methods*
  • Estrone / analogs & derivatives*
  • Estrone / pharmacokinetics
  • Female
  • Humans
  • Image Enhancement / methods
  • Metabolic Clearance Rate
  • Organ Specificity
  • Organotechnetium Compounds / pharmacokinetics*
  • Polyglutamic Acid / pharmacokinetics*
  • Positron-Emission Tomography / trends*
  • Rabbits
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Inbred F344
  • Receptors, Estrogen / metabolism*
  • Tissue Distribution


  • Biomarkers, Tumor
  • Organotechnetium Compounds
  • Radiopharmaceuticals
  • Receptors, Estrogen
  • technetium 99m polyglutamate 3-aminoethyl estradiol
  • Polyglutamic Acid
  • Estrone