The estrogen receptor present in many breast tumors and targets regions of the brain offers a mechanism by which estrogens, suitably labeled with appropriate radionuclides, might be taken up, thereby providing an image of the tumor or target area. We have succeeded in preparing estrogens labeled with the positron-emitter fluorine-18 and have demonstrated that large, receptor-positive tumors and affected axillary lymph nodes can be imaged very effectively. The thrust of this proposal is to extend the sensitivity of these agents to small, receptor-poor tumors, (1) by enhancing their binding selectivity (specific to non-specific binding ratio) by incorporating substituents known to raise receptor binding or lower lipophilicity, and (2) by controlling their metabolism and clearance by providing a hydroxyl group for direct conjugation (phase II directed agents) or by incorporating the F-18 at a metabolically labile site (diagnostic soft drugs). The receptor and non-specific binding of these agents will be evaluated in vitro and their target site uptake efficiency and selectivity and the extent of metabolite generation and recirculation will be studied in rats in vivo. Finally, novel approaches to radiofluorination of arene and enol systems will be studied: fluoride ion addition or substitution of arene complexes with iron or manganese and an oxidative fluorination approach utilizing chemical, anodic or photochemical means to achieve reaction of fluoride ions with arene or enol cation radicals or dications. The successful development of selective and effective tumor and brain estrogen receptor imaging agents would be useful: It would aid in evaluating the extent of breast tumor invasion and metastasis, provide a prognostic indicator for hormone therapy, and assist in evaluating estrogen effects on behavior.

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National Cancer Institute (NCI)
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Biochemical Endocrinology Study Section (BCE)
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University of Illinois Urbana-Champaign
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Zhou, Dong; Xu, Jinbin; Mpoy, Cedric et al. (2018) Preliminary evaluation of a novel 18F-labeled PARP-1 ligand for PET imaging of PARP-1 expression in prostate cancer. Nucl Med Biol 66:26-31
Zhou, Dong; Chu, Wenhua; Voller, Thomas et al. (2018) Copper-Mediated Nucleophilic Radiobromination of Aryl Boron Precursors: Convenient Preparation of a Radiobrominated PARP-1 Inhibitor. Tetrahedron Lett 59:1963-1967
Zhou, Dong; Kim, Sung Hoon; Chu, Wenhua et al. (2017) Evaluation of aromatic radiobromination by nucleophilic substitution using diaryliodonium salt precursors. J Labelled Comp Radiopharm 60:450-456
Fowler, Amy M; Clark, Amy S; Katzenellenbogen, John A et al. (2016) Imaging Diagnostic and Therapeutic Targets: Steroid Receptors in Breast Cancer. J Nucl Med 57 Suppl 1:75S-80S
Chan, Szeman Ruby; Fowler, Amy M; Allen, Julie A et al. (2015) Longitudinal noninvasive imaging of progesterone receptor as a predictive biomarker of tumor responsiveness to estrogen deprivation therapy. Clin Cancer Res 21:1063-70
Bosch, Ana; Li, Zhiqiang; Bergamaschi, Anna et al. (2015) PI3K inhibition results in enhanced estrogen receptor function and dependence in hormone receptor-positive breast cancer. Sci Transl Med 7:283ra51
Yasui, Norio; Mayne, Christopher G; Katzenellenbogen, John A (2015) Preparation of o-Fluorophenols from Nonaromatic Precursors: Mechanistic Considerations for Adaptation to Fluorine-18 Radiolabeling. Org Lett 17:5540-3
Paterni, Ilaria; Bertini, Simone; Granchi, Carlotta et al. (2015) Highly selective salicylketoxime-based estrogen receptor ? agonists display antiproliferative activities in a glioma model. J Med Chem 58:1184-94
Zhou, Dong; Chu, Wenhua; Peng, Xin et al. (2015) Facile purification and click labeling with 2-[(18)F]fluoroethyl azide using solid phase extraction cartridges. Tetrahedron Lett 56:952-954
Paterni, Ilaria; Granchi, Carlotta; Katzenellenbogen, John A et al. (2014) Estrogen receptors alpha (ER?) and beta (ER?): subtype-selective ligands and clinical potential. Steroids 90:13-29

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