title: Comparison of cyclic RGD peptides for αvβ3 integrin detection in a rat model of myocardial infarction.
abstract: BACKGROUND
  Expression of αvβ3 integrin is increased after myocardial infarction as part of the repair process. Increased expression of αvβ3 has been shown by molecular imaging with 18F-galacto-RGD in a rat model. The 68Ga-labelled RGD compounds 68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 have high specificity and affinity, and may therefore serve as alternatives of 18F-galacto-RGD for integrin imaging.
  
  
  METHODS
  Left coronary artery ligation was performed in rats. After 1 week, rats were imaged with [13N]NH3, followed by 18F-galacto-RGD, 68Ga-NODAGA-RGD or 68Ga-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 β3 expression (as part of the αvβ3 receptor).
  
  
  RESULTS
  In vivo imaging showed focal RGD uptake in the hypoperfused area of infarcted myocardium as defined with [13N]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 18F-galacto-RGD, 5.2 ± 0.8 for 68Ga-NODAGA-RGD, and 4.1 ± 0.7 for 68Ga-TRAP(RGD)3. The 68Ga-NODAGA-RGD ratio was higher compared to 68Ga-TRAP(RGD)3 (p = 0.04), but neither of the 68Ga tracers differed from 18F-galacto-RGD (p > 0.05). The area of augmented 68Ga-RGD uptake was associated with β3 integrin expression (CD61).
  
  
  CONCLUSIONS
  68Ga-NODAGA-RGD and 68Ga-TRAP(RGD)3 uptake was equally increased in the infarct area at 1 week post infarction as 18F-galacto-RGD. These results show the potential of 68Ga-labelled RGD peptides to monitor integrin expression as a part of myocardial repair and angiogenesis after ischaemic injury in vivo.
authors.affiliation: Department of Nuclear Medicine, Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, Munich 81675, Germany. iina.laitinen@gmail.com.
authors.forename: Iina
authors.initials: I
authors.lastname: Laitinen
authors.forename: Johannes
authors.initials: J
authors.lastname: Notni
authors.forename: Karolin
authors.initials: K
authors.lastname: Pohle
authors.forename: Martina
authors.initials: M
authors.lastname: Rudelius
authors.forename: Eliane
authors.initials: E
authors.lastname: Farrell
authors.forename: Stephan G
authors.initials: SG
authors.lastname: Nekolla
authors.forename: Gjermund
authors.initials: G
authors.lastname: Henriksen
authors.forename: Stefanie
authors.initials: S
authors.lastname: Neubauer
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger