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.
Original language | English (US) |
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Pages (from-to) | 354-362 |
Number of pages | 9 |
Journal | European Journal of Nuclear Medicine and Molecular Imaging |
Volume | 34 |
Issue number | 3 |
DOIs | |
State | Published - Mar 2007 |
Keywords
- Biodistribution
- ERK1/2
- Endometriosis
- Tc-GAP-EDL
- Tumor imaging
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
MD Anderson CCSG core facilities
- Small Animal Imaging Facility