S-EPMC6321344 - Evaluation of [<sup>68</sup>Ga]Ga-DOTA-TCTP-1 for the Detection of Metalloproteinase 2/9 Expression in Mouse Atherosclerotic Plaques. - OmicsDI

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Evaluation of [⁶⁸Ga]Ga-DOTA-TCTP-1 for the Detection of Metalloproteinase 2/9 Expression in Mouse Atherosclerotic Plaques.

ABSTRACT: Background: The expression of matrix metalloproteinases 2/9 (MMP-2/9) has been implicated in arterial remodeling and inflammation in atherosclerosis. We evaluated a gallium-68 labeled peptide for the detection of MMP-2/9 in atherosclerotic mouse aorta. Methods: We studied sixteen low-density lipoprotein receptor deficient mice (LDLR^-/-ApoB^100/100) kept on a Western-type diet. Distribution of intravenously-injected MMP-2/9-targeting peptide, [⁶⁸Ga]Ga-DOTA-TCTP-1, was studied by combined positron emission tomography (PET) and contrast-enhanced computed tomography (CT). At 60 min post-injection, aortas were cut into cryosections for autoradiography analysis of tracer uptake, histology, and immunohistochemistry. Zymography was used to assess MMP-2/9 activation and pre-treatment with MMP-2/9 inhibitor to assess the specificity of tracer uptake. Results: Tracer uptake was not visible by in vivo PET/CT in the atherosclerotic aorta, but ex vivo autoradiography revealed 1.8 ± 0.34 times higher tracer uptake in atherosclerotic plaques than in normal vessel wall (p = 0.0029). Tracer uptake in plaques correlated strongly with the quantity of Mac-3-positive macrophages (R = 0.91, p < 0.001), but weakly with MMP-9 staining (R = 0.40, p = 0.099). Zymography showed MMP-2 activation in the aorta, and pre-treatment with MMP-2/9 inhibitor decreased tracer uptake by 55% (p = 0.0020). Conclusions: The MMP-2/9-targeting [⁶⁸Ga]Ga-DOTA-TCTP-1 shows specific uptake in inflamed atherosclerotic lesions; however, a low target-to-background ratio precluded in vivo vascular imaging. Our results suggest, that the affinity of gelatinase imaging probes should be steered towards activated MMP-2, to reduce the interference of circulating enzymes on the target visualization in vivo.

SUBMITTER: Kiugel M

PROVIDER: S-EPMC6321344 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Evaluation of [<sup>68</sup>Ga]Ga-DOTA-TCTP-1 for the Detection of Metalloproteinase 2/9 Expression in Mouse Atherosclerotic Plaques.

Kiugel Max M Hellberg Sanna S Käkelä Meeri M Liljenbäck Heidi H Saanijoki Tiina T Li Xiang-Guo XG Tuomela Johanna J Knuuti Juhani J Saraste Antti A Roivainen Anne A

Molecules (Basel, Switzerland) 20181201 12

<i>Background</i>: The expression of matrix metalloproteinases 2/9 (MMP-2/9) has been implicated in arterial remodeling and inflammation in atherosclerosis. We evaluated a gallium-68 labeled peptide for the detection of MMP-2/9 in atherosclerotic mouse aorta. <i>Methods</i>: We studied sixteen low-density lipoprotein receptor deficient mice (LDLR<sup>-/-</sup>ApoB<sup>100/100</sup>) kept on a Western-type diet. Distribution of intravenously-injected MMP-2/9-targeting peptide, [<sup>68</sup>Ga]Ga ...[more]

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