Abstract
BackgroundThe aim of this study was to compare contrast enhancement of Magnevist® (gadopentate dimeglumine (Mag)) to that of PEGylated Magnevist®-loaded liposomal nanoparticles (Mag-Lnps) in pancreatic cancer patient-derived xenograft (PDX) mouse model via magnetic resonance imaging (MRI).MethodsMag-Lnps formulated by thin-film hydration and extrusion was characterized for the particle size and zeta potential. A 21.1 T vertical magnet was used for all MRI. The magnet was equipped with a Bruker Advance console and ParaVision 6.1 acquisitions software. Mag-Lnps phantoms were prepared and imaged with a 10-mm birdcage coil. For in vivo imaging, animals were sedated and injected with a single dose (4 mg/kg) of Mag or Mag-Lnps with Mag equivalent dose. Using a 33-mm inner diameter birdcage coil, T1 maps were acquired, and signal to noise ratio (SNR) measured for 2 h.ResultsMag-Lnps phantoms showed a remarkable augmentation in contrast with Mag increment. However, in in vivo imaging, no significant difference in contrast was observed between Mag and MRI. While Mag-Lnps was observed to have fairly high tumor/muscle (T/M) ratio in the first 30 min, free Mag exhibited higher T/M ratio over the time-period between 30 and 120 min. Overall, there was no statistically significant difference between Mag and Mag-Lnp in rating MR image quality. Low payload of Mag entrapment by Lnps and restricted access of water (protons) to Mag-Lnps may have affected the performance of Mag-Lnps as an effective contrast agent.ConclusionThis study showed no significance difference in MRI contrast between Mag and Mag-Lnp pancreatic cancer PDX mouse models.
Highlights
The aim of this study was to compare contrast enhancement of M agnevist® (gadopentate dimeglumine (Mag)) to that of PEGylated Magnevist®-loaded liposomal nanoparticles (Mag-Lnps) in pancreatic cancer patientderived xenograft (PDX) mouse model via magnetic resonance imaging (MRI)
To ascertain if nanoparticle-loaded contrast agents would exhibit higher contrast than free contrast agent in an unperturbed solid tumor environment, a comparative study was conducted on MR imaging of tumors using free Mag and Mag-Lnp
Mag, which was approved by Food and Drug Administration (FDA), has been widely used in clinical practices as MRI contrast agent (Raatschen et al 2006), Mag has exhibited some limitations such as short blood circulation time, relatively low relaxivity and potential toxicity, for example, nephrogenic systemic fibrosis
Summary
The aim of this study was to compare contrast enhancement of M agnevist® (gadopentate dimeglumine (Mag)) to that of PEGylated Magnevist®-loaded liposomal nanoparticles (Mag-Lnps) in pancreatic cancer patientderived xenograft (PDX) mouse model via magnetic resonance imaging (MRI). A circumspective review of traditional contrast agents which are usually gadolinium-based contrast agents (GBCA) has revealed that these agents are nonspecific and undergo rapid extravasation into extracellular compartment with rapid elimination from the body (Aime and Caravan 2009; Ghaghada et al 2009). Another pertinent challenge which precludes traditional imaging in MRI with GBCA is the difficulty in detecting tumors with diameter 1 cm or less due to low resolution (Fisher et al 2001). To improve on contrast enhancement of such tumors, functionalized and biocompatible nano-delivery system with high payload of gadolinium (Gd) can deliver and retain high level of gadolinium (Gd) through enhanced permeation and retention (EPR) effect that exists preferentially in tumors (Dewi et al 2013)
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