title: Nanoparticle PET-CT detects rejection and immunomodulation in cardiac allografts.
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.
  
  
  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.
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ueno
authors.forename: Partha
authors.initials: P
authors.lastname: Dutta
authors.forename: Edmund
authors.initials: E
authors.lastname: Keliher
authors.forename: Florian
authors.initials: F
authors.lastname: Leuschner
authors.forename: Maulik
authors.initials: M
authors.lastname: Majmudar
authors.forename: Brett
authors.initials: B
authors.lastname: Marinelli
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Thomas
authors.initials: T
authors.lastname: Christen
authors.forename: Filip K
authors.initials: FK
authors.lastname: Swirski
authors.forename: Peter
authors.initials: P
authors.lastname: Libby
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D003301:Copper Radioisotopes; D004656:Enalapril / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006084:Graft Rejection / Q000000981:diagnostic imaging* / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006321:Heart / Q000000981:diagnostic imaging* / Q000187:drug effects; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008264:Macrophages / Q000000981:diagnostic imaging / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D064847:Multimodal Imaging; D009206:Myocardium / Q000276:immunology*; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D013997:Time Factors; D014057:Tomography, X-Ray Computed
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D003301:Copper Radioisotopes; D007166:Immunosuppressive Agents; D019275:Radiopharmaceuticals; D004656:Enalapril
keywords: heart transplantation; imaging; macrophage; positron emission tomography/computed tomography