Office of Technology Transfer – University of Michigan

Photo-Acoustic Tomography, PAT contrast agent, Rheumatoid Arthritis, Clofazimine

Technology #6731

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Researchers
Rahul K. Keswani
Managed By
Ed Pagani
Assistant Director, Health Technologies 734-763-3558
Patent Protection
US Patent Pending 2016-0220710

Rheumatoid arthritis (RA) is the inflammation of the lining of the membranes that surround your joints which can eventually destroy the cartilage and bone within the joint. The number of people globally with RA was 73 million in 2014. Macrophages are central to the pathophysiology of arthritic inflammation and are at the origin of pathological bone erosion in arthritic conditions. Current therapeutics such as TNF inhibitors and IL-1RA attempt to dampen the inflammatory response, however when systemically injected are poised to affect the whole body indiscriminately and therefore have many side effects.

Novel non-invasive imaging technics need to be developed for monitoring the treatment of RA. Photo-Acoustic Tomography (PAT) is a hybrid imaging technique whereby non-ionizing laser pulses are used to generate ultrasonic emission from biological tissues followed by detection via ultrasonic transducers and computational algorithms to form images. PAT contrast agents need to be developed that can enhance the signal-to-noise ratio of the imaged organ/tissue. Therefore, macrophage-targeted PAT contrast agents would offer valuable guidance during the diagnosis and therapy of the arthritic conditions.

Development of PAT contrast agent and RA therapeutic

Imagine if a small molecule reagent could act both as a PAT contrast and as therapeutic specifically targeting macrophages that are critical in RA pathogenesis. This may be possible with modifications of a drug that has already been developed and has been used for decades. Clofazimine have been found to massively bioaccumulate in macrophages to the point that they precipitate out, forming insoluble intracellular drug inclusions. We call these precipitates – crystal-like-drug-inclusions (CLDIs). This generates an anti-inflammatory response and these CLDIs can be used as a contrast agent for PAT.

Applications

  • Photo-Acoustic Imaging and Theranostic Therapy of Rheumatoid Arthritis
  • Photo-Acoustic Visualization of Macrophages

Advantages

  • Non-invasive diagnostic for RA
  • Anti-Inflammatory Activity of CFZ
  • Known pharmacokinetics, pharmacology and toxicology of CFZ in humans
  • Long half-life
  • Macrophage specific targeting reducing side effects