Diagnostic PET Imaging of Mammary Microcalcifications Using 64 Cu-DOTA-Alendronate in a Rat Model of Breast Cancer.

Autor:	Ahrens BJ; Deparment of Molecular Immunology, Beckman Research Institute of the City of Hope, Duarte, California.; Division of Comparative Medicine, Beckman Research Institute of the City of Hope, Duarte, California.; Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, California., Li L; Deparment of Molecular Immunology, Beckman Research Institute of the City of Hope, Duarte, California., Ciminera AK; Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, California.; Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, California., Chea J; Deparment of Molecular Immunology, Beckman Research Institute of the City of Hope, Duarte, California., Poku E; Deparment of Molecular Immunology, Beckman Research Institute of the City of Hope, Duarte, California., Bading JR; Department of Medical Oncology, City of Hope, Duarte, California; and., Weist MR; Deparment of Molecular Immunology, Beckman Research Institute of the City of Hope, Duarte, California.; Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, California., Miller MM; Department of Cell and Molecular Biology, Beckman Research Institute of the City of Hope, Duarte, California., Colcher DM; Deparment of Molecular Immunology, Beckman Research Institute of the City of Hope, Duarte, California., Shively JE; Deparment of Molecular Immunology, Beckman Research Institute of the City of Hope, Duarte, California jshively@coh.org.
Jazyk:	angličtina
Zdroj:	Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2017 Sep; Vol. 58 (9), pp. 1373-1379. Date of Electronic Publication: 2017 Apr 27.
DOI:	10.2967/jnumed.117.190850
Abstrakt:	The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64 Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64 Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64 Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague-Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64 Cu-DOTA-alendronate. Results: 64 Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64 Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64 Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64 Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64 Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as well as the differentiation of malignant versus benign tumors based on absolute labeling uptake. (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze:	MEDLINE
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