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

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.