New Imaging Kit for Assessment of Estrogen Receptors with Single Photon Emission Computed Tomography

摘要

To evaluate the feasibility of using 99mTc-glutamate peptide- estradiol (GAP-EDL) in imaging estrogen receptor positive (ER +) diseases. Methods: 3-Aminoethyl estradiol (EDL) was conjugated glutamate peptide (GAP) to yield GAP-EDL. Cellular uptake studies of 99mTc-GAP-EDL were conducted in ER (+) cell lines (MCF7, 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 13762 breast tumor-bearing rats at 0.5- 4 hrs. Each rat was administered 99mTc-GAP-EDL (10 microCi/rat, 10 microgm/rat, iv). Two animal models (Rats and rabbits) were created to ascertain whether cellular or tumor uptake by 99mTc-GAP-EDL was via an ER-mediated process, In tumor model, breast tumor-bearing rats were pretreated with diethylstilbestrol (DES, n=3, 10 mg/kg, iv) 1 hr prior to receiving 99mTc-GAP-EDL (300 microCi/rat, iv). In endometriosis model, part of rabbit uterine tissue was dissected and grafted in the peritoneal wall. The rabbit was administered with 99mTc-GAP-EDL (1 mCi/rabbit, iv). Results: There was 10-40% decreased uptake in cells treated with DES or tamoxifen compared to untreated 99mTc-GAP-EDL. 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 in 99mTc-GAP groups at 4 hrs. In 99mTc-GAP-EDL, ROI analysis of images showed that tumor-to muscle ratios were decreased in blocking groups. In endometriosis model, the grafted uterine tissue could be visualized by 99mTc-GAP-EDL. Conclusion: A new imaging kit for assessment of estrogen receptors with single photon emission computed tomography (SPECT) was developed. Cellular or tumor uptake of 99mTc-GAPEDL was via an estrogen receptor-mediated process. 99mTc GAP-EDL is a useful ER (+) imaging agent.