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 Babich, J. W. Articles by Fischman, A. J. Search for Related Content PubMed PubMed Citation Articles by Babich, J. W. Articles by Fischman, A. J.

Localization of Radiolabeled Chemotactic Peptide at Focal Sites of Escherichia coli Infection in Rabbits: Evidence for a Receptor-Specific Mechanism

Division of Nuclear Medicine of the Department of Radiology, and the Trauma Service of the Department of Surgery, Massachusetts General Hospital and Shriners Burns Institute, Boston, Massachusetts

Correspondence: For correspondence or reprints contact: Alan J. Fischman, MD, PhD, Division of Nuclear Medicine, Massachusetts General Hospital, Boston, MA 02114.

ABSTRACT

The infection imaging properties of a high-affinity ^99mTc-labeled chemotactic peptide receptor agonist (N-formyl-methionyl-leucyl-phenylalanine-lysine; N-For-MLFK) were compared with a low-affinity agonist (N-Acetyl-MLFK; N-Ac-MLFK), a moderate-affinity antagonist (N-isobutyloxycarbonyl-MLFK; N-iBoc-MLFK) and nonspecific inflammation imaging agents. Methods: All peptides were prepared by solid-phase methods and purified by high-performance liquid chromatography. The products were assayed in vitro for N-formyl-methionyl-leucyl-phenylalanine receptor binding and superoxide production. Three types of studies were performed in rabbits with Escherichia coli infection: (Study A) Four groups of six animals were coinjected with ^99mTc-N-For-MLFK-hydrazinonicoti-namide (N-For-MLFK-HYNIC) plus ¹¹¹In-immunoglobulin G, ¹¹¹In-red blood cells or ¹¹¹In-diethylene triamine pentaacetic acid. (Study B) Three groups of six rabbits were coinjected with ¹¹¹In-leukocytes plus ^99mTc-N-For-MLFK-HYNIC, ^99mTc-N-Ac-MLFK-HYNIC or ^99mTc-N-iBoc-MLFK-HYNIC. (Study C) Two groups of six rabbits were injected with ^99mTc-N-For-MLFK-HYNIC and ¹¹¹In-leukocytes with and without an excess of antagonist. In all three studies, the radiopharmaceuticals were injected 24 hr after infection and dual photon (^99mTc and ¹¹¹In) gamma camera images were acquired at 2-3 and 16-18 hr later. Target-to-background (T/B) ratios were calculated for regions of interest drawn over the infected and contralateral normal tissue. Results: N-For-MLFK, N-Ac-MLFK and N-iBoc-MLFK had EC₅₀s for receptor binding of 2.0, 830 and 150 nM, respectively. The corresponding EC₅₀s for superoxide production were 20.0, 10³ and >10⁴. Study A demonstrated that the T/B for ^99mTc-N-For-MLFK-HYNIC was higher than for any of the nonspecific imaging agents (p <0.001), and ¹¹¹In-immunoglobulin G had a higher T/B ratio than ¹¹¹In-diethylenetriamine pentaacetic acid (p < 0.01) or ¹¹¹In-red blood cells (p = NS). Study B showed that ^99mTc-N-For-MLFK-HYNIC had a higher T/B ratio than the other peptides (p < 0.001). ¹¹¹In-leukocytes and ^99mTc-N-iBoc-MLFK-HYNIC had comparable T/B ratios, which were higher than for ^99mTc-N-Ac-MLFK-HYNIC (p <0.05). Study C demonstrated that coinjection with an antagonist resulted in a significant reduction in the T/B ratio for ^99mTc-N-For-MLFK-HYNIC (p <0.001), but did not affect the T/B ratio for ¹¹¹In-leukocytes. Conclusion: Nonspecific mechanisms contribute minimally to the localization of ^99mTc-chemotactic peptide analogs at sites of infection and the majority of the accumulation appears to be receptor mediated. Also, chemotactic peptide receptor antagonists can be used for infection imaging. These results provide important new insights for future radio-pharmaceutical development.

Key Words: agonist • antagonists • peptide • chemotactic infection

This article has been cited by other articles:

				W. Hartwig, E. A. Carter, R. E. Jimenez, J. Werner, A. J. Fischman, C. F.-D. Castillo, and A. L. Warshaw Chemotactic peptide uptake in acute pancreatitis: correlation with tissue accumulation of leukocytes J Appl Physiol, August 1, 1999; 87(2): 743 - 749. [Abstract] [Full Text] [PDF]