Because of radiocolloids’ “very heterogeneous composition,” they move out from the injection site “slowly and in some ways randomly,” Mark Pykett, VMD, PhD, CEO of Navidea Biopharmaceuticals told “It generally takes 2 to 3 hours. Because a large amount of the larger particle size material is retained at the injection site, you can get ‘shine-through’ and overlap which can mask the underlying positive lymph node, causing confusion between the signal and the injection site.”

Smaller molecules should more rapidly clear from the injection site, reducing shine-through problems. The smaller and more uniform molecular size of Navidea’s radiolabeled SLN imaging agent, Lymphoseek® (technetium Tc-99m tilmanocept) Injection, allows quicker clearance than seen with radiocolloids, says Dr. Pykett.

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Lymphoseek is a Tc-99m labeled dextran-mannose conjugate that remains in the SLN for longer than radiolabeled colloids because its mannose components bind to the cell surface CD206 receptors of immune system macrophages that accumulate within SLNs.1,2 It is used intraoperatively with a portable gamma detector.

Since Lymphoseek binds strongly to surface receptors on macrophages that congregate within lymph nodes, its molecules tend to remain in the first lymph node they encounter, differentiating SLNs from other, downstream nodes that might not need to be biopsied.  No currently available lymphatic imaging agents can identify nodes harboring tumor cells per se, but Lymphoseek’s rapid clearance and strong surface receptor binding offer improved specificity for identifying SLNs, Dr. Pykett said.

“Lymphoseek is like a homing device that allows you to track the key lymph nodes—the so-called sentinel lymph nodes—that are more likely to harbor cancer if cancer has in fact spread from the primary site,” Dr. Pykett said. “This is the first and only agent that has been specifically designed or purpose-built to pinpoint the key predictive lymph nodes that are important for biopsy and can assess if cancer has spread into the lymphatic system. This is the first agent that uses a receptor-targeted mechanism to precisely identify and pinpoint those key lymph nodes.”

For patients, that should improve staging accuracy and appropriate therapies, Dr. Pykett added.

Shine-through is “not nearly” the problem with Lymphoseek as it can be with radiocolloids, agreed Anne M. Wallace, MD, Team Leader for breast cancer at the University of San Diego Moores Cancer Center, La Jolla, CA and lead author of a study that included two phase 3 clinical trials comparing Lymphoseek with blue dye for SLN detection, which was published online March 17 in the Annals of Surgical Oncology.1

“Because it is a small molecule, it drains from the injection site really quickly, so you don’t get as much scatter,” she said. “Then it binds to a specific lymph node so it doesn’t continue to drain downstream.”