Virtual tumor biopsies?

If you have cancer today, finding out how advanced the tumor has become often requires an invasive biopsy and precious time to prepare and analyze cancerous cells in the lab. Sanford-Burnham’s Dr. Masanobu Komatsu sees another way to rapidly diagnose what’s happening deep inside you.

Someday, he envisions, your doctor will simply administer a solution of nanoparticles that contain a fluorescent dye and a chemical address that helps them home to the tumor cells in your body. The dye will have unique physical properties that enable imaging inside the tissue. A laser device will then beam infrared light into the tumor site, exciting the fluorescent dye that has accumulated in the cancer cells. A computer monitor will display an image of the tumor with cell-by-cell resolution.

None of this will require a scratch, and your doctor will be able to quickly grade the tumor—rapidly assessing how advanced your cancer has grown and how best to attack it.

Sounds like science fiction? A new collaborative study by Dr. Komatsu and Dr. Kevin Belfield, a chemist at the University of Central Florida, suggests that the technology might be closer than you think.

In a recent paper published in the journal Bioconjugate Chemistry, the two teams describe a new strategy for using an advanced fluorescence imaging technique called two-photon fluorescence microscopy to more effectively resolve the details of a hidden tumor.

In the study, nanoparticles encapsulating a light-emitting dye were injected into mice bearing tumors.

“The idea was not just to develop a dye, but to develop a dye that illuminates tumors,” says Dr. Komatsu. Tumor cells express a lot of folate receptors—molecules on the cell surface that bind folic acid. So Drs. Komatsu and Belfield engineered their nanoparticles so that a folic acid derivative coats their surfaces. The resulting nanoprobes showed high selectivity for the tumor, and they traveled from tumor blood vessels directly into tumor cells.

Two-photon fluorescence microscopy, which minimizes light scattering in tissue, provided 3D, cellular-level resolution up to 350 micrometers (or 0.35 millimeters) deep in the tumors. And the researchers are now getting even deeper—up to 1.5 millimeters. The technique produces images along focal planes—essentially making cross-section images of the tumor—and that information is used to reconstruct the tumor in 3D, Dr. Komatsu says.

Dr. Belfield had been developing the technique for several years, but he wanted to test his technology in a living organism. Dr. Komatsu, who studies the blood vessels that feed tumors in mice, is working on new ways to halt cancer growth. The pair met in 2008 at a Sanford-Burnham seminar, and they decided to refine Dr. Belfield’s technology for use in a mouse model.

The study in Bioconjugate Chemistry demonstrates a proof-of-concept that the two researchers will continue to develop. “The ultimate goal for this collaborative research is to develop a method for what we call ‘virtual histology,’” Dr. Komatsu says.

But advancing the technology could someday lead to more than just a diagnostic tool. Drs. Komatsu and Belfield believe the nanoprobes could carry therapeutic drugs directly to cancer cells as effectively as they now carry the fluorescent dye.

The day may not be too far off when physicians will not only image a malignant tumor in a living patient, they’ll also be able to see it in real time as anti-cancer drugs destroy it. Now there would be a movie with a happy ending.

Read more about this collaboration in the Orlando Sentinel: UCF, Sanford-Burnham collaborations help build on promise of Lake Nona’s Medical City

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Original Paper:

Wang X, Morales AR, Urakami T, Zhang L, Bondar MV, Komatsu M, & Belfield KD (2011). Folate receptor-targeted aggregation-enhanced near-IR emitting silica nanoprobe for one-photon in vivo and two-photon ex vivo fluorescence bioimaging. Bioconjugate chemistry, 22 (7), 1438-50 PMID: 21688841

ResearchBlogging.org

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