title: Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques.
abstract: OBJECTIVE
  Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of (99m)Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits).
  
  
  METHODS
  Anti-MT1-MMP monoclonal IgG(3) and negative control IgG(3) were radiolabelled with (99m)Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield (99m)Tc-MT1-MMP mAb and (99m)Tc-IgG(3), respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed.
  
  
  RESULTS
  (99m)Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional (99m)Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while (99m)Tc-IgG(3) accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest (99m)Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID×BW/mm(2) × 10(2)), followed in decreasing order by fibroatheromatous (1.8 ± 1.3), collagen-rich (1.6 ± 1.0) and neointimal lesions (1.5 ± 1.5). In contrast, (99m)Tc-IgG(3) accumulation was almost independent of the histological grade of lesions.
  
  
  CONCLUSIONS
  Higher (99m)Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with (99m)Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required.
authors.affiliation: Department of Patho-functional Bioanalysis, Kyoto University, Kyoto, Japan. kuge@ric.hokudai.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Nozomi
authors.initials: N
authors.lastname: Takai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Kantaro
authors.initials: K
authors.lastname: Nishigori
authors.forename: Seigo
authors.initials: S
authors.lastname: Ishino
authors.forename: Junko
authors.initials: J
authors.lastname: Kamihashi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000276:immunology*; D057054:Molecular Imaging / Q000379:methods*; D009525:Niacin / Q000737:chemistry; D015609:Organotechnetium Compounds; D058226:Plaque, Atherosclerotic / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015609:Organotechnetium Compounds; D009525:Niacin; D053511:Matrix Metalloproteinase 14