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