Comparison of cyclic RGD peptides for αvβ3 integrin detection in a rat model of myocardial infarction

被引:48
作者
Laitinen, Iina [1 ]
Notni, Johannes [2 ]
Pohle, Karolin [1 ]
Rudelius, Martina [3 ]
Farrell, Eliane [1 ]
Nekolla, Stephan G. [1 ]
Henriksen, Gjermund [1 ]
Neubauer, Stefanie [4 ,5 ]
Kessler, Horst [4 ,5 ,6 ]
Wester, Hans-Juergen [2 ]
Schwaiger, Markus [1 ]
机构
[1] Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-81675 Munich, Germany
[2] Tech Univ Munich, Pharmaceut Radiochem, D-85748 Garching, Germany
[3] Tech Univ Munich, Inst Pathol, D-81675 Munich, Germany
[4] Tech Univ Munich, IAS, Dept Chem, D-85748 Garching, Germany
[5] Tech Univ Munich, Ctr Integrated Prot Sci CIPSM, D-85748 Garching, Germany
[6] King Abdulaziz Univ, Fac Sci, Dept Chem, Jeddah 21589, Saudi Arabia
关键词
F-18-galacto-RGD; Ga-68-NODAGA-RGD; Ga-68-TRAP(RGD)(3); PET; Myocardial infarction; EXPRESSION; TRAP; ALPHA-V-BETA-3; ANGIOGENESIS; CONFORMATION; TRACERS; LIGANDS; CELLS; HEART;
D O I
10.1186/2191-219X-3-38
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
100231 [临床病理学]; 100902 [航空航天医学];
摘要
Background: Expression of alpha(v)beta(3) integrin is increased after myocardial infarction as part of the repair process. Increased expression of alpha(v)beta(3) has been shown by molecular imaging with F-18-galacto-RGD in a rat model. The Ga-68-labelled RGD compounds Ga-68-NODAGA-RGD and Ga-68-TRAP(RGD) 3 have high specificity and affinity, and may therefore serve as alternatives of F-18-galacto-RGD for integrin imaging. Methods: Left coronary artery ligation was performed in rats. After 1 week, rats were imaged with [N-13]NH3, followed by F-18-galacto-RGD, Ga-68-NODAGA-RGD or Ga-68-TRAP(RGD) 3 using a dedicated animal PET/CT device. Rats were killed, and the activity in tissues was measured by gamma counting. The heart was sectioned for autoradiography and histology. Immunohistochemistry was performed on consecutive sections using CD31 for the endothelial cells and CD61 for beta(3) expression (as part of the alpha(v)beta(3) receptor). Results: In vivo imaging showed focal RGD uptake in the hypoperfused area of infarcted myocardium as defined with [N-13] NH3 scan. In autoradiography images, augmented uptake of all RGD tracers was observed within the infarct area as verified by the HE staining. The tracer uptake ratios (infarct vs. remote) were 4.7 +/- 0.8 for F-18-galacto-RGD, 5.2 +/- 0.8 for Ga-68-NODAGA-RGD, and 4.1 +/- 0.7 for Ga-68-TRAP(RGD) 3. The Ga-68-NODAGA-RGD ratio was higher compared to Ga-68-TRAP(RGD) 3 (p = 0.04), but neither of the Ga-68 tracers differed from F-18-galacto-RGD (p > 0.05). The area of augmented Ga-68-RGD uptake was associated with beta 3 integrin expression (CD61). Conclusion: Ga-68-NODAGA-RGD and Ga-68-TRAP(RGD) 3 uptake was equally increased in the infarct area at 1 week post infarction as F-18-galacto-RGD. These results show the potential of Ga-68-labelled RGD peptides to monitor integrin expression as a part of myocardial repair and angiogenesis after ischaemic injury in vivo.
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页码:1 / 9
页数:9
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