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Myeloperoxidase Activity Imaging Using 67Ga Labeled Substrate

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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 67Ga-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 67Ga, 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 67Ga–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

67Ga–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 67Ga–I interaction with the target enzyme.

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Acknowledgments

Partial support for this study was provided by the RSNA Research and Education Foundation (JWC) and the NIH [P50-CA86355, R01-HL078641 (RW), and R01 EB000858 (AB)].

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Authors and Affiliations

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

    Manel Querol Sans & Alexei A. Bogdanov Jr

  2. Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA, 02129, USA

    John W. Chen & Ralph Weissleder

Authors
  1. Manel Querol Sans
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  2. John W. Chen
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  3. Ralph Weissleder
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  4. Alexei A. Bogdanov Jr
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Corresponding author

Correspondence to Alexei A. Bogdanov Jr.

Additional information

M. Querol and J. W. Chen contributed equally to this work.

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Querol Sans, M., Chen, J.W., Weissleder, R. et al. Myeloperoxidase Activity Imaging Using 67Ga Labeled Substrate. Mol Imaging Biol 7, 403–410 (2005). https://doi.org/10.1007/s11307-005-0020-5

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  • DOI: https://doi.org/10.1007/s11307-005-0020-5

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