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PubMed · 16292477

Myeloperoxidase activity imaging using (67)Ga labeled substrate.

Manel Querol Sans·John W Chen·Ralph Weissleder·Alexei A Bogdanov
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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.

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AnimalsChromatography, High Pressure LiquidGallium RadioisotopesKineticsMaleMiceMice, Inbred C57BLMolecular StructurePeroxidaseSpectrum AnalysisSubstrate SpecificityTomography, X-Ray ComputedJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov't

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Manel Querol Sans, John W Chen, Ralph Weissleder, Alexei A Bogdanov. Myeloperoxidase activity imaging using (67)Ga labeled substrate.. https://doi.org/10.1007/s11307-005-0020-5

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