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Circ Cardiovasc Imaging. 2013 Jul;6(4):568-73. doi: 10.1161/CIRCIMAGING.113.000481. Epub 2013 Jun 14.

Nanoparticle PET-CT detects rejection and immunomodulation in cardiac allografts.

Author information

1
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

Abstract

BACKGROUND:

Macrophages predominate among the inflammatory cells in rejecting allografts. These innate immune cells, in addition to allospecific T cells, can damage cardiomyocytes directly.

METHODS AND RESULTS:

We explored whether sensitive positron emission tomography-computed tomography (PET-CT) imaging of macrophages-avid nanoparticles detects rejection of heart allografts in mice. In addition, we used the imaging method to follow the immunomodulatory impact of angiotensin-converting enzyme inhibitor therapy on myeloid cells in allografts. Dextran nanoparticles were derivatized with the PET isotope copper-64 and imaged 7 days after transplantation. C57BL/6 recipients of BALB/c allografts displayed robust positron emission tomography signal (standard uptake value allograft, 2.8±0.3; isograft control, 1.7±0.2; P<0.05). Autoradiography and scintillation counting confirmed the in vivo findings. We then imaged the effects of angiotensin-converting enzyme inhibitor (5 mg/kg enalapril). Angiotensin-converting enzyme inhibitor significantly decreased nanoparticle signal (P<0.05). Histology and flow cytometry showed a reduced number of myeloid cells in the graft, blood, and lymph nodes and diminished antigen presentation (P<0.05 versus untreated allografts). Angiotensin-converting enzyme inhibitor also significantly prolonged allograft survival (12 versus 7 days; P<0.0001).

CONCLUSIONS:

Nanoparticle macrophage PET-CT detects heart transplant rejection and predicts organ survival by reporting on myeloid cells.

KEYWORDS:

heart transplantation; imaging; macrophage; positron emission tomography/computed tomography

PMID:
23771986
PMCID:
PMC3734553
DOI:
10.1161/CIRCIMAGING.113.000481
[Indexed for MEDLINE]
Free PMC Article

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