New Imaging Technology Could Improve Bladder-Cancer Detection

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Researchers have developed a new strategy that they say could detect bladder cancer with more accuracy and sensitivity than standard endoscopy methods. Endoscopy refers to a procedure in which surgeons use an instrument equipped with a lens to see inside the patient. The researchers identified a protein known as CD47 as a molecular imaging target to distinguish bladder cancer from benign tissues. In the future, this technique could improve bladder cancer detection, guide more precise cancer surgery and reduce unnecessary biopsies, therefore increasing cancer patients' quality of life.
The work is published in Science Translational Medicine.

Bladder cancer, the fifth most common cancer in the United States, is generally identified in the clinic by a procedure called cystoscopy, an endoscopy in the bladder. Then in the operating room, surgeons remove the cancerous tissue for biopsy. This form of cancer must be monitored closely because it has one of the highest recurrence rates of all cancers. It is important that cystoscopy imaging be both highly sensitive (able to detect subtle cancer) and specific (able to distinguish between benign and cancerous tumors) so surgeons can remove cancerous tissue at an early stage to prevent invasion into the underlying muscle, which may require complete removal of the bladder.

However, standard cystoscopy has insufficient sensitivity and specificity, particularly for flat-appearing cancers that blend in with the bladder and may be confused with inflammation. To improve the specificity of the imaging, the researchers needed something that would distinguish cancer cells from benign cells. They needed a target, which they found in CD47, a protein on a cell's surface that signals the immune system not to attack the cell. Most cells produce it, but cancer makes a lot more CD47 than normal cells.
The researchers added a fluorescent molecule to an antibody that binds to CD47. The modified antibodies were then introduced into intact bladders, which had been surgically removed from patients with invasive bladder cancer. Because the bladders were kept in good condition, the study's imaging methods mirrored the process a urologist might use with a real patient.
After 30 minutes, they rinsed the bladder, so only the antibodies that bound to the CD47 protein remained. When the tumor was exposed to fluorescent light, the cancer cells "lit up" whereas normal or inflamed cells did not.
The researchers successfully tested two fluorescent tags and imaging technology combinations. They attached the molecule fluorescein isothiocynate, which glows in the presence of white light, to the anti-CD47 antibody and introduced it into the bladder. Then, they used confocal endomicroscopy, an instrument that shines white light and takes high-resolution images of the bladder. They also attached a fluorescent molecule quantum dot to the anti-CD47 antibody that glows in the presence of blue light. Then they used blue light cystoscopy to make an image of the bladder.
The researchers performed biopsies of 119 tissue samples from 26 bladders. They removed 35 tissue regions that glowed pink (cancerous) and 84 tissue regions that did not (noncancerous). The samples were also sent and analyzed by a pathologist that was blinded to the imaging diagnoses. Overall, they found the sensitivity of cancer detection to be 82.9 percent and the specificity to be 90.5 percent.
A candidate anti-CD47 antibody for therapeutic use in human cancers is currently being tested in a small clinical trial; clinical-grade imaging technologies are already available; and the whole-organ imaging approach closely mimics how a surgeon could use the method in patients. But before putting the technique into practice, the anti-CD47 antibody/fluorescent molecule would need to be approved for this purpose by the U.S. Food and Drug Administration.