Cationic Contrast Agents for Computed Tomography Imaging of Tissues

 

INV-20021

Early diagnosis of degenerative joint diseases like osteoarthritis (OA) is critical because it gives a narrow window of time to reverse disease progression. While computed tomography (CT) can diagnose changes in subchondral bone, it is not clinically viable for imaging joint soft tissues like cartilage that exhibit early degenerative changes associated with OA onset. CT is developed for soft tissue imaging by using radio-opaque contrast agents injected into the joint. Contrast agents like ioxaglate (IOX) are anionic and thus repelled by negatively charged cartilage that hinders their intra-tissue penetration and partitioning resulting in poor CT attenuation. This is further complicated by their short intra-tissue residence time owing to rapid clearance from joints. Higher doses are therefore required to enhance flux and achieve intra-cartilage concentrations sufficient for CT imaging, which results in both local and systemic toxicity. 

 

In this invention, Northeastern researchers have created positively charged contrast agents that, due to electrostatic interactions, can rapidly penetrate cartilage through its full thickness in very high concentrations such that a high CT signal is possible with a small concentration of the contrast agent. It is a novel idea achieved by designing an optimally charged multi-arm avidin (mAv) and cationic peptide carriers (CPC+8) that can rapidly penetrate through the full thickness of cartilage in high concentrations using weak-reversible electrostatic interactions. It is then used to develop cationic nano-charged contrast agents (NCAs) for CT imaging of cartilage. CCAs (Cationic Contrast Agents) achieved a similar CT signal with 160x lower concentration of anionic IOX, and thus can significantly minimize toxicity associated with a high dose of IOX. Intra-cartilage spatial distribution of CCAs correlates strongly with the density of negatively charged groups, which shows that CCAs can enable the diagnosis of early OA and its staging.

 

- Enables early diagnosis of OA and it's staging

- Enables high CT signal with 160x lower concentration of contrast agent 3 to reduce toxicity

- Enables rapid penetration into the cartilage reducing patient hospital time 

- This method does not negatively affect cartilage

- Can be used for a variety of other negatively charged tissues

 

- Applications in joint soft tissue imaging using CT

- Applications in early diagnosis of OA and its staging

- Applications in drug delivery to cartilage

- Applications can be extended to imaging and drug delivery in a wide range of negatively charged tissues like meniscus, intervertebral discs, mucosal membrane, eye, fracture callus etc.

- Optimally charged carriers can be used for making other cellular derived materials like exosomes cartilage targeting

 

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