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Noninvasive optical and PET imaging of cartilage loss and cancer cell death using carrier free 89Zr: high sensitivity and imaging contrast


Stanford Reference:

12-443


Abstract


Stanford researchers have developed a non-invasive, dual modality probe using Carrier free 89Zr for early diagnosis and therapy monitoring of cartilage-related diseases, such as osteoarthritis. Carrier free 89Zr provides a new, convenient radioactive imaging and optical imaging method to monitor cartilage loss in various cartilage related diseases in early stages, before symptoms become apparent. Physicians can diagnose and treat cartilage-related diseases early before significant damage occurs. This invention can also be used to monitor and assess the response to cartilage repair strategies. Imaging studies using Carrier free 89Zr showed high sensitivity and good imaging contrast of healthy to osteoarthritis cartilage.
In addition, carrier free 89Zr could be used for the detection of cancer cell apoptosis (such as Epidemoid carcinoma and bone cancer when cell death was confirmed ex vivo). Cancer cell death is a fundamental biological process that is present in cancer disease pathologies. Imaging probes that can determine, noninvasively, the amount and type of cell death in tumors may have utility in clinical prognosis of tumor pathogenesis and potential deep tissue imaging of cancer in humans.

Figures

Figure 1 description - Carrier free 89Zr was administrated for the early detection of cartilage degenerated osteoarthritis (OA) in dual modality imaging (PET & Cerenkov imaging). Different retention values between sham side and OA side were observed from day 3 to day 7 post-injection (p.i.), respectively. The peak ratio (sham vs. OA) was showed at day 5 p.i. Representative imaging in vivo and ex vivo was shown. Whereas, carrier free 18F and 64Cu showed no different in knee joint signal values at the 1h, 2h, 4h and 24h time point data not shown here).

Figure 2 description - Carrier free 89Zr was administrated for the early detection of cancer cell death in PET imaging. Eptidermoid carcinoma (A 431 cell line), Bone cancer (143B cell line) showed high accumulation from 1h p.i. to day 7 p.i. Peak uptake was demonstrated in 4h p.i. (representative data showed in figure 2). Severe cell death was then confirmed by later ex vivo study (data not shown here). As comparation, prostate cancer cell (PC3) showed very low uptake than eptidermoid carcinoma and bone cancer (figure 2). Low cell death was also then confirmed ex vivo (data not shown here).

Stage of Research
  • Proof-of-concept
  • Carrier free 89Zr was neutralized and formulated for intravenous injection prior to in vivo PET and Cerenkov fluorescence imaging
  • Both modalities obtained high sensitivity and good imaging contrast of healthy to osteoarthritis cartilage, comparing with MRI
  • Lower signal to degenerated cartilage, confirmed by ex-vivo biopsy
  • Detect cancer (such as epidemoid carcinoma and bone cancer) in their early stage, when cell death happened.
  • Monitor the cancer therapy through detect the cancer cell death

  • Applications


    • Non-invasive early diagnosis and therapy monitoring of cartilage-related diseases
    • Imaging cartilage related disease in different subjects including human, research animal models and other substance
    • Imaging cancer diseases
    • Drug development (cartilage disease & cancer)
    • Clinical prognosis evaluation of cancer process and therapy

    Advantages


    • Real-time non invasive monitoring of cartilage-related disease
    • Easy purification of final product
    • High uptake, high sensitivity, high resolution and high healthy cartilage/degenerated cartilage contrast ratio
    • High accumulation in cartilage and fast clearance from other tissues
    • Provides very early detection before symptoms are apparent of cartilage related diseases
    • Surface and deep cancer cell death early detection and therapy monitor in cancer research and potential clinical application
    • Clinical prognosis evaluation of cancer process and therapy with such easy-preparing isotope

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    Date Released

     10/31/2013
     

    Licensing Contact


    Irit Gal, Senior Licensing Associate
    650-723-1586 (Business)
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    Related Keywords


    musculoskeletal   osteoarthritis   rheumatoid arthritis   Imaging: PET   Cerenkov imaging   cartilage   Carrier free Zr89   bone disease   bone disorders   bone imaging   healthcare: imaging   Imaging agents   imaging probe   imaging: contrast agent   imaging: CT   imaging: molecular   in vivo imaging   molecular imaging   optical imaging   optical imaging agent   optical imaging contrast agent   optical molecular imaging   medical devices: diagnostics and measurement   medical devices: imaging   fluorescence imaging   Fluorescent Molecular Tomography   fluorescent probes   
     

       

      

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