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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

To evaluate the feasibility of using 99mTc-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 99mTc-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 99mTc-GAP-EDL. Two animal models (rats and rabbits) were created to ascertain whether tumor uptake of 99mTc-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 99mTc-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 99mTc-GAP-EDL.

Results

There was a 10–40% reduction in uptake of 99mTc-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 99mTc-GAP-EDL groups were significantly higher than those in 99mTc-GAP groups at 4 h. Among 99mTc-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 99mTc-GAP-EDL.

Conclusion

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

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Acknowledgements

The authors wish to thank Eloise Daigle for her secretarial support. This work was supported in part by MDACC sponsored research grant (LS2005-00012824PL, Mr. Kazuhiko Sugiura, Methods, Ltd., Tokyo, Japan) and the United States Army Department of Defense Breast Cancer Research Grant Concept Award (DoD BCRP W81XWH-04-1-06-24). The animal research is supported by M.D. Anderson Cancer Center (CORE) Grant NIH CA-16672.

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Authors and Affiliations

  1. Division of Diagnostic Imaging, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Nobukazu Takahashi, David J. Yang, Saady Kohanim, Chang-Sok Oh, Dong-Fang Yu, Ali Azhdarinia, Hiroaki Kurihara & E. Edmund Kim

  2. Division of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Xiaochun Zhang & Joe Y. Chang

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  1. Nobukazu Takahashi
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Correspondence to David J. Yang.

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Takahashi, N., Yang, D.J., Kohanim, S. et al. Targeted functional imaging of estrogen receptors with 99mTc-GAP-EDL. Eur J Nucl Med Mol Imaging 34, 354–362 (2007). https://doi.org/10.1007/s00259-006-0191-6

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  • DOI: https://doi.org/10.1007/s00259-006-0191-6

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