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Molecular MR imaging of neovascular progression in the Vx2 tumor with ?v?3-targeted paramagnetic nanoparticles.


ABSTRACT:

Purpose

To assess the dependence of neovascular molecular magnetic resonance (MR) imaging on relaxivity (r1) of ?v?3-targeted paramagnetic perfluorocarbon (PFC) nanoparticles and to delineate the temporal-spatial consistency of angiogenesis assessments for individual animals.

Materials and methods

Animal protocols were approved by the Washington University Animal Studies Committee. Proton longitudinal and transverse relaxation rates of ?v?3-targeted and nontargeted PFC nanoparticles incorporating gadolinium diethylenetrianime pentaacedic acid (Gd-DTPA) bisoleate (BOA) or gadolinium tetraazacyclododecane tetraacetic acid (Gd-DOTA) phosphatidylethanolamine (PE) into the surfactant were measured at 3.0 T. These paramagnetic nanoparticles were compared in 30 New Zealand White rabbits (four to six rabbits per group) 14 days after implantation of a Vx2 tumor. Subsequently, serial MR (3.0 T) neovascular maps were developed 8, 14, and 16 days after tumor implantation by using ?v?3-targeted Gd-DOTA-PE nanoparticles (n = 4) or nontargeted Gd-DOTA-PE nanoparticles (n = 4). Data were analyzed with analysis of variance and nonparametric statistics.

Results

At 3.0 T, Gd-DTPA-BOA nanoparticles had an ionic r1 of 10.3 L · mmol(-1) · sec(-1) and a particulate r1 of 927000 L · mmol(-1) · sec(-1). Gd-DOTA-PE nanoparticles had an ionic r1 of 13.3 L · mmol(-1) · sec(-1) and a particulate r1 of 1?197000 L · mmol(-1) · sec(-1). Neovascular contrast enhancement in Vx2 tumors (at 14 days) was 5.4% ± 1.06 of the surface volume with ?v?3-targeted Gd-DOTA-PE nanoparticles and 3.0% ± 0.3 with ?v?3-targeted Gd-DTPA-BOA nanoparticles (P = .03). MR neovascular contrast maps of tumors 8, 14, and 16 days after implantation revealed temporally consistent and progressive surface enhancement (1.0% ± 0.3, 4.5% ± 0.9, and 9.3% ± 1.4, respectively; P = .0008), with similar time-dependent changes observed among individual animals.

Conclusion

Temporal-spatial patterns of angiogenesis for individual animals were followed to monitor longitudinal tumor progression. Neovasculature enhancement was dependent on the relaxivity of the targeted agent.

SUBMITTER: Schmieder AH 

PROVIDER: S-EPMC3721054 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Molecular MR imaging of neovascular progression in the Vx2 tumor with αvβ3-targeted paramagnetic nanoparticles.

Schmieder Anne H AH   Winter Patrick M PM   Williams Todd A TA   Allen John S JS   Hu Grace G   Zhang Huiying H   Caruthers Shelton D SD   Wickline Samuel A SA   Lanza Gregory M GM  

Radiology 20130614 2


<h4>Purpose</h4>To assess the dependence of neovascular molecular magnetic resonance (MR) imaging on relaxivity (r1) of αvβ3-targeted paramagnetic perfluorocarbon (PFC) nanoparticles and to delineate the temporal-spatial consistency of angiogenesis assessments for individual animals.<h4>Materials and methods</h4>Animal protocols were approved by the Washington University Animal Studies Committee. Proton longitudinal and transverse relaxation rates of αvβ3-targeted and nontargeted PFC nanoparticl  ...[more]

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