Functional Imaging of Estrogen Receptors with Radiolabeled-GAP-EDL in Rabbit Endometriosis Model

Takahashi N, Nobukazu Takahashi, Yang DJ, David J. Yang, Hiroaki Kurihara, Kurihara H, Agatha Borne, Borne A, Saady Kohanim, Kohanim S, Chang-Sok Oh, Oh CS, Chang‐Sok Oh, Osama Mawlawi, Mawlawi O, E. Edmund Kim, Kim EE
Academic radiology · 2007 · vol. 14(9) , pp. 1050–1057 · doi:10.1016/j.acra.2007.05.020 · PMID:17707312 · W2057017098
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This study investigated the utility of radiolabeled-GAP-EDL as a functional imaging agent for estrogen receptors in a rabbit model of endometriosis.

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Abstract

Rationale and objectivesEndometriosis is a common women's health problem. Animal models provide an invaluable tool to study the natural history of endometriosis. We previously have reported that (99m)Tc-labeled glutamate peptide-estradiol ((99m)Tc-GAP-EDL) is a useful agent for imaging functional estrogen receptor (ER) via an ER-mediated process. This study was to evaluate the feasibility of using radiolabeled GAP-EDL to image ER-positive (ER +) endometriosis in nonprimate animal models.Materials and methods3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. In vitro cellular uptake studies of (99m)Tc and (68)Ga-GAP-EDL inhibition with cold estrone were conducted in 13,762 rat mammary tumor cells. To create a rabbit model with endometriosis, part of uterine tissue was dissected and grafted in the peritoneal wall. Eight weeks after surgery, scintigraphic images were obtained after intravenous injection of (99m)Tc-GAP-EDL (1 mCi/rabbit, intravenous) at 0.5-2.0 hours, and (68)Ga-GAP-EDL at 45 minutes. We also performed (68)Ga-GAP-EDL blocking study in rabbit model by using tamoxifen. The rabbits were sacrificed and the grafts were excised for histologic examination.ResultsIn vitro uptake study of (99m)Tc- and (68)Ga-GAP-EDL in 13,762 rat breast cancer cells showed gradually increasing uptake of both tracers. Accumulation of (68)Ga-GAP-EDL in 13,762 cells was inhibited with cold estrone in a dose-dependent manner. In the endometriosis model, the grafted uterine tissue could be visualized by (99m)Tc-GAP-EDL. Necropsy was performed at 2.5 hours after injection time. Four follicular endometrial lesions in eight implanted endometrial tissues were detected, and all lesions could be detected by (99m)Tc-GAP-EDL. Planar scintigraphy of uterus, ovary and implants of necropsy specimen revealed an increased uptake of (99m)Tc-GAP-EDL in comparison with surrounding abdominal wall tissue. Microscopic examinations support that (99m)Tc-GAP-EDL was accumulated in the microinvasive endometrial tissue. After blocking with tamoxifen, (68)Ga-GAP-EDL accumulation in the endometrial grafts could not be visualized, and endometrial tissue-to-normal tissue count ratios were statistically higher in a nonblocked image than that in the blocked image.ConclusionsEndometriosis uptake of radiolabeled GAP-EDL was via an estrogen receptor-mediated process. Radiolabeled-GAP-EDLs are useful agents for imaging endometriosis.

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Condition tags

endometriosis

MeSH descriptors

Disease Models, Animal Endometriosis Endometriosis Endometrium Endometrium Estrone Organotechnetium Compounds Polyglutamic Acid Receptors, Estrogen Animals Endometriosis Endometrium Estrone Estrone Female Organotechnetium Compounds Polyglutamic Acid Rabbits Radionuclide Imaging Radiopharmaceuticals

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