Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques.
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.
Kuge
Yuji
Y
Department of Patho-functional Bioanalysis, Kyoto University, Kyoto, Japan. kuge@ric.hokudai.ac.jp
Takai
Nozomi
N
Ogawa
Yuki
Y
Temma
Takashi
T
Zhao
Yan
Y
Nishigori
Kantaro
K
Ishino
Seigo
S
Kamihashi
Junko
J
Kiyono
Yasushi
Y
Shiomi
Masashi
M
Saji
Hideo
H
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
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015609:Organotechnetium Compounds; D009525:Niacin; D053511:Matrix Metalloproteinase 14