HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hwang, D.-R. Articles by Welch, M.J. Search for Related Content PubMed PubMed Citation Articles by Hwang, D.-R. Articles by Welch, M.J.

Positron-Labeled Angiotensin-Converting Enzyme (ACE) Inhibitor: Fluorine-18-Fluorocaptopril. Probing the ACE Activity In Vivo by Positron Emission Tomography

Edward Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri
Bristol-Myers-Squibb Pharmaceutical Research Institute, Princeton, New Jersey

Correspondence: For reprints contact: Michael J. Welch. PhD, Mallinckrodt Institute of Radiology, Washington University Medical School, Division of Radiation Sciences, 510 South Kingshighway Blvd., Box 8131, St. Louis, MO 63110.

ABSTRACT

To evaluate the feasibility of probing the distribution of angiotensin-converting enzyme (ACE) in vivo using positron emission tomography (PET), 4-cis-[¹⁸F]fluorocaptopril (¹⁸FCAP) was prepared by the reaction of the triflate 2 with K¹⁸F/Kryptofix 222 in MeCN followed by hydrolysis (2 N NaOH). The synthesis time was 1 hr with an average radiochemical yield (EOS) of 12% and a specific activity of >300 Ci/mmol. In vivo biodistribution in rats at 30 min after administration showed high uptakes into organs known to have high ACE concentration (lung, kidney and aorta) and faster clearance of ¹⁸FCAP for lung and kidney, compared to the clearance from the aorta. When different amounts of unlabeled 4-cis-fluoro-captopril (SQ 25750) were coinjected in rats, a dose of > 5 µg/kg decreased the lung uptake by one-half while only 1 µg/kg decreased the kidney uptake by one-half. In general, the binding in the four tissues studied was saturable with the expected capacity. ¹⁸FCAP was administered to a human and displaceable uptake observed in the lung and kidney. The results demonstrate the feasibility of probing ACE in vivo using PET.

This article has been cited by other articles:

				F. J. Femia, K. P. Maresca, S. M. Hillier, C. N. Zimmerman, J. L. Joyal, J. A. Barrett, O. Aras, V. Dilsizian, W. C. Eckelman, and J. W. Babich Synthesis and Evaluation of a Series of 99mTc(CO)3+ Lisinopril Complexes for In Vivo Imaging of Angiotensin-Converting Enzyme Expression J. Nucl. Med., June 1, 2008; 49(6): 970 - 977. [Abstract] [Full Text] [PDF]

				Y. Chandrashekhar and J. Narula Exposing ACE up the Sleeve... J. Nucl. Med., February 1, 2007; 48(2): 173 - 174. [Full Text] [PDF]

				V. Dilsizian, W. C. Eckelman, M. L. Loredo, E. M. Jagoda, and J. Shirani Evidence for Tissue Angiotensin-Converting Enzyme in Explanted Hearts of Ischemic Cardiomyopathy Using Targeted Radiotracer Technique J. Nucl. Med., February 1, 2007; 48(2): 182 - 187. [Abstract] [Full Text] [PDF]

				S. M. Danilov, V. D. Gavrilyuk, F. E. Franke, K. Pauls, D. W. Harshaw, T. D. McDonald, D. J. Miletich, and V. R. Muzykantov Lung uptake of antibodies to endothelial antigens: key determinants of vascular immunotargeting Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1335 - L1347. [Abstract] [Full Text] [PDF]

				F. QING, T. J. McCARTHY, J. MARKHAM, and D. P. SCHUSTER Pulmonary Angiotensin-converting Enzyme (ACE) Binding and Inhibition in Humans . A Positron Emission Tomography Study Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 2019 - 2025. [Abstract] [Full Text]