Functional Imaging of Estrogen Receptors with Radiolabeled-GAP-EDL in Rabbit Endometriosis Model
| Autor: | Nobukazu Takahashi, E. Edmund Kim, Saady Kohanim, David J. Yang, Agatha Borne, Chang Sok Oh, Hiroaki Kurihara, Osama Mawlawi |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Pathology animal structures Estrone medicine.drug_class Endometriosis Uterus Estrogen receptor Ovary Endometrium chemistry.chemical_compound Internal medicine medicine Animals Radiology Nuclear Medicine and imaging Radionuclide Imaging Mammary tumor business.industry musculoskeletal neural and ocular physiology Organotechnetium Compounds musculoskeletal system medicine.disease Disease Models Animal medicine.anatomical_structure Endocrinology Polyglutamic Acid Receptors Estrogen chemistry Estrogen Female Rabbits Radiopharmaceuticals business tissues Tamoxifen medicine.drug |
| Zdroj: | Academic Radiology. 14:1050-1057 |
| ISSN: | 1076-6332 |
| Popis: | Rationale and Objectives Endometriosis 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 99mTc-labeled glutamate peptide-estradiol (99mTc-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 Methods 3-Aminoethyl estradiol (EDL) was conjugated to glutamate peptide (GAP) to yield GAP-EDL. In vitro cellular uptake studies of 99mTc and 68Ga-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 99mTc-GAP-EDL (1 mCi/rabbit, intravenous) at 0.5–2.0 hours, and 68Ga-GAP-EDL at 45 minutes. We also performed 68Ga-GAP-EDL blocking study in rabbit model by using tamoxifen. The rabbits were sacrificed and the grafts were excised for histologic examination. Results In vitro uptake study of 99mTc- and 68Ga-GAP-EDL in 13,762 rat breast cancer cells showed gradually increasing uptake of both tracers. Accumulation of 68Ga-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 99mTc-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 99mTc-GAP-EDL. Planar scintigraphy of uterus, ovary and implants of necropsy specimen revealed an increased uptake of 99mTc-GAP-EDL in comparison with surrounding abdominal wall tissue. Microscopic examinations support that 99mTc-GAP-EDL was accumulated in the microinvasive endometrial tissue. After blocking with tamoxifen, 68Ga-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. Conclusions Endometriosis uptake of radiolabeled GAP-EDL was via an estrogen receptor-mediated process. Radiolabeled-GAP-EDLs are useful agents for imaging endometriosis. |
| Databáze: | OpenAIRE |
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