New Screening Method Scans Surface Veins for Circulating Tumor Cells

| November 5, 2007

Researchers say they can detect circulating tumor cells using multiphoton intravital flow cytometry without drawing blood. "This new technique is less invasive and can evaluate a much larger volume of blood than what can be drawn from a patient for analysis," senior author Philip Low, PhD, the Ralph C Corley Distinguished Professor of Chemistry at Purdue University, in West Lafayette, Indiana, told Medscape.

The findings appear in the July 10 issue of the Proceedings of the National Academy of Sciences. In a news release publicizing the study, Dr. Low noted that in the initial stages of cancer, there can be few circulating tumor cells.

"By increasing the volume of blood analyzed, we improve the sensitivity of the test and allow for earlier diagnosis. If there are 2 cancer cells in every 50 mL of blood, odds are the cells would not be found in a 10-mL blood sample. However, the cells would be found in the 100 mL of blood that flow through large veins each minute," he said.

The new screening method involves the intravenous injection of a tumor-specific fluorescent ligand followed by multiphoton fluorescence imaging of superficial blood vessels such as those on the wrist or cheek. When targeted by the laser, which scans across the diameter of the blood vessel 1000 times per second, the tumor cells glow and can be quantified.

The investigators performed the in vivo flow detection on a 2-photon fluorescence microscope. The technology is able to scan every cell that is pumped through the vessel.

The research team developed 2 injectable labeling agents that attach to different cancers. One label targets ovarian, non–small-cell lung, kidney, and endometrial cancer, and the other targets prostate cancer. The first label has already been tested in humans and, according to Dr. Low, has no adverse effects and could potentially be administered weekly.

Questions Remain Regarding Safety

"Circulating tumor cells provide a benchmark for disease progression, and precise monitoring of their levels could lead to personalized treatment," Dr. Low said.

Coauthor Ji-Xin Cheng, PhD, an assistant professor of chemistry and biomedical engineering, also from Purdue, suggests that optical imaging offers high resolution and chemical specificity for cancer detection but tends to suffer from limited penetration depth, making it hard to reach tumors inside the body. "In vivo detection of circulating tumor cells in surface veins provides an excellent way to overcome this problem," Dr. Cheng added.

During an interview with Medscape, Dr. Low said many believe that techniques such as this offer a more sensitive method of detecting tumor cells and may soon help physicians identify which patients can avoid or perhaps undergo less chemotherapy.

"We’re hoping that this new method will help clinicians and patients avoid the many chemotherapy-induced side effects such as hair loss, gut bleeds, bone-marrow suppression, and risk of opportunistic infections."

Dr. Low says that while his group has demonstrated efficacy, questions remain regarding safety. The dyes must be shown to be completely nontoxic, he added. "It will take us some time to get through the US Food and Drug Administration process."

The researchers report having no significant financial relationships.

Proc Natl Acad Sci. 2007;104:11760-11765.

Category: In-vivo

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