Assessment and Biodistribution of a Dual Ultrasound Contrast and Photoacoustic Imaging Agent

This study by Yosra Toumia et al. advances the knowledge of the behavior of a hybrid system consisting of pristine graphene anchored polyvinyl alcohol microbubbles (G/PVA MB), and is a proof concept for their efficiency as contrast agents in photoacoustic as well as ultrasound imaging.

Article Summary:

  • The main issues to address when designing a biomedical device are its biocompatibility, chemical versatile, and efficiency for one or more specific imaging modalities; aiming to better diagnosis and support a potential therapy.
  • Polymeric PVA MBs were chosen as an ultrasound contrast agent due to their lipidic counterparts leading to high stability and surface chemical versatility for multimodal imaging and potential use as a theranostic agent.
  • These capabilities can also be conveyed on the hybrid graphene/MBs (G/MBs) system to obtain photoacoustic (PAI) enhancer properties.
  • The hybrid system was optimized using spacers with different lengths between the graphene moiety and the MB surface, including poly(ethylene glycol) (PEG) chains, to better understand the toxic effect of the system on cells and on the PAI performance.
  • Performed multispectral photoacoustic imaging to differentiate endogenous and exogenous contrast and quantified the kinetics and biodistribution of the graphene PVA MBs in specific organs.
  • This is the first study showing the whole body biodistribution of a pristine graphene hybrid medical contrast agent using a commercial photoacoustic setup.
  • The G/PVA-PEGDA2000 microbubbles also show significant Non Linear Contrast efficacy in ultrasound imaging.


This system constitutes a step toward developing a multimodal contrast agent and a versatile platform for molecular imaging, which can be implemented with targeting agents and/or drugs for a therapy translation.

The authors have demonstrated that incorporating a PEG-based diamine intermediate spacer for the tethering of graphene onto the PVA MBs shows better microbubble dispersibility and enhances the biocompatibility of the hybrid contrast agent as tested on fibroblast NIH 3T3 cells.

They plan to continue developing and optimizing these G/PVA MBs, as they represent a great potential in PAI and are keen to engineer their surface with bioactive molecules. Studies are ongoing to determine the targeting, drug loading, and delivery capabilities of this device for applications in cancer therapy.

Toumia Y, Cerroni B, Trochet P, Lacerenza S, Oddo L, Domenici F, et al. Performances of a Pristine Graphene-Microbubble Hybrid Construct as Dual Imaging Contrast Agent and Assessment of Its Biodistribution by Photoacoustic Imaging. Part Part Syst Charact [Internet]. 2018 May 29;1800066:1800066. Available from: