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- Title
Targeted functional imaging of estrogen receptors with <sup>99m</sup>Tc-GAP-EDL.
- Authors
Takahashi, Nobukazu; Yang, David J.; Kohanim, Saady; Chang-Sok Oh; Dong-Fang Yu; Azhdarinia, Ali; Kurihara, Hiroaki; Xiaochun Zhang; Chang, Joe Y.; Kim, E. Edmund
- Abstract
To evaluate the feasibility of using 99mTc-glutamate peptide-estradiol in functional imaging of estrogen receptor-positive [ER(+)] diseases. 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. 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. 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.
- Subjects
ESTROGEN receptors; LABORATORY animals; MEDICAL imaging systems; ESTRADIOL; PHOSPHORYLATION; WESTERN immunoblotting
- Publication
European Journal of Nuclear Medicine & Molecular Imaging, 2007, Vol 34, Issue 3, p354
- ISSN
1619-7070
- Publication type
Article
- DOI
10.1007/s00259-006-0191-6