Contrast-enhanced MRI of murine sponge model for progressive angiogenesis assessed with gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/1).
OBJECTIVE
To investigate the potential value of MRI for noninvasive assessment of angiogenesis in a murine model exploiting the properties of two contrast agents, gadoteridol (ProHance) and gadocoletic acid trisodium salt (B22956/1).


METHODS
Biocompatible sponges were implanted in both mice flanks. Stimulated sponges contained human recombinant basic fibroblast growth factor (bFGF) as the angiogenic agent; control sponges contained vehicle. Angiogenesis was evaluated by MRI after injection of extravascular (ProHance) or blood-pool (B22956/1) contrast agents at different times after sponge implantation. Sponges signal intensity enhancement was calculated both as the relative enhancement and the rate of relative enhancement. Results from MRI were validated by classic biochemical (hemoglobin level and protein content) and morphological (histology) assays.


RESULTS
The intrinsic different properties of ProHance and B22956/1 in wash-in and wash-out kinetics were useful to detect progressive vascularization and the establishment of a functional vascular network in the implants. Moreover, MRI allowed the appreciation of differences in neovessel colonization between bFGF-treated sponges and controls. Hemoglobin level, protein content, and histology confirmed the sponge vascularization and MRI results.


CONCLUSIONS
Contrast-enhanced MRI is a reliable tool to study vascular characteristics in animal models of angiogenesis. The different kinetic properties of contrast agents can provide evidence of different functional neovascularization aspects and levels.
Ramponi
Simona
S
Pharmacological Department, Bracco Imaging SpA, Milan Research Centre, Milan, Italy. simona.ramponi@bracco.com
Rebaudengo
Cristina
C
Cabella
Claudia
C
Grotti
Adriana
A
Vultaggio
Stefania
S
Aime
Silvio
S
Morisetti
Alberto
A
Lorusso
Vito
V
D000818:Animals; D001672:Biocompatible Materials; D003287:Contrast Media; D004195:Disease Models, Animal; D016222:Fibroblast Growth Factor 2; D005682:Gadolinium; D006571:Heterocyclic Compounds; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000175:diagnosis* / Q000473:pathology; D009942:Organometallic Compounds; D015503:Surgical Sponges
C440468:B-22956-1; D001672:Biocompatible Materials; D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D016222:Fibroblast Growth Factor 2; D005682:Gadolinium