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Mol Imaging Biol. 2005 Nov-Dec;7(6):403-10.

Myeloperoxidase activity imaging using (67)Ga labeled substrate.

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  • 1Department of Radiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA.

Abstract

PURPOSE:

The aim of the study is to assess the feasibility of imaging specific activity of myeloperoxidase (MPO), a leukocyte enzyme with important roles in inflammation and atherosclerosis, by single photon emission computed tomography (SPECT) using a novel (67)Ga-labeled radiotracer obtained by conjugating desferrioxamine (DF) and hydroxyindolyl acetic acid in vivo.

MATERIALS AND METHODS:

A reducing substrate of MPO (I) was synthesized by reacting commercially available DF with 2-(5-hydroxy-1H-indol-3-yl) acetic acid in the presence of a coupling agent [dicyclohexyl carbodiimide (DCC)]. The chelating unit was labeled with (67)Ga, and its interaction with MPO was characterized using MALDI-TOF and UV-vis. Mice with Matrigel implants containing human MPO were used to model diseased tissues rich in MPO. Three hours after the injection of (67)Ga-I, SPECT/computed tomography (CT) imaging was performed on a high-resolution Gamma Medica X-SPECT system. Biodistribution studies were performed six hours after the injection of the radiotracer.

RESULTS:

The feasibility of compound I oligomerization in the presence of MPO and MPO-mediated cross-linking with proteins was initially confirmed in vitro. In vivo, a 2.7-fold increase in target-to-muscle ratio could be measured in MPO-containing Matrigel implants in mice. Biodistribution experiments demonstrated a 60% increase of radioactivity in MPO-containing vs. control (contralateral) Matrigel implants.

CONCLUSION:

(67)Ga-I can be used to image MPO activity in a model system. The accumulation mechanism is based on a differential pharmacokinetics because of the size increase resulting from (67)Ga-I interaction with the target enzyme.

PMID:
16292477
[PubMed - indexed for MEDLINE]
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