Lighting the Way to Detect Tumors During Surgery

In 2010, a company called On Target Laboratories, based in West Lafayette, Indiana, was founded with the goal of helping doctors find cancers more easily during surgery. Their first product was CYTALUX (pafolacianine), a molecule that makes even the tiniest of tumors glow brightly in the operating room. Today, surgeons are finding tumors in lungs and ovaries more easily using this first-of-its kind tool. But the path to bring CYTALUX from the laboratory into the operating room took a lot of persistence from the small start-up company—a journey that was helped along with support from NCI’s Small Business Innovation Research (SBIR) program.

Seeing the need for innovation 

Sumith Kularatne, Ph.D., vice president of research and development for On Target, was part of the original team that envisioned the potential of a tool like CYTALUX. Having lost his grandfather to cancer when he was a young boy in Sri Lanka, Sumith has spent much of his life blending his love of chemistry with a strong desire to help families affected by cancer. This led him to the United States, where he eventually began researching molecules that could help reveal cancer cells during surgery in real time.

“Surgeons are dealing with a challenging situation,” Sumith explained. Sometimes, a tumor is buried underneath the surface of an organ, rendering it invisible to the naked eye. At other times, a tumor may be too small or not solid enough for a surgeon to feel it with their fingers or surgical instruments. These pitfalls, he continued, inspired On Target to develop a technology that could enhance the surgeon’s sense of sight—like a pair of tumor-revealing glasses.

Advancing innovative research and technologies is the goal of NCI’s SBIR program, which funds researcher-initiated projects that align with NCI’s mission. Through the federal SBIR program, small businesses can receive funding, resources, and other support to help drive innovative technologies like CYTALUX into the marketplace to benefit patients.

Making tumors glow

CYTALUX is a modified version of folate, commonly known as vitamin B9, that is attached to a fluorescent dye. There are many more folate receptors on the surface of certain tumors than on surrounding cells in the body. This overabundance of folate receptors provides a target that researchers can use to shuttle cargo, such as the fluorescent dye in CYTALUX, to a tumor’s location.

Once CYTALUX binds to folate receptors and enters tumor cells, a special camera used during surgery causes the dye to emit a bright green signal. This approach, the team found, worked well in animal models of ovarian cancer, the cancer type with the largest concentration of folate receptors.

A logical next step was to test CYTALUX in lung cancer, which has a high proportion of folate receptors and causes more deaths in the United States than any other cancer. While surgery remains the gold standard for treating early-stage lung cancers, as many as a third to half of these cancers return, likely because some tumors or tumor cells remained behind after the initial surgery.

With limited funding options for the highly experimental work, the On Target team competed for and received a phase 1 SBIR grant to study CYTALUX for lung cancer in animal models. Two years later, with promising data in hand, the group received an additional phase 2 SBIR award to conduct more studies and scale up production of CYTALUX.

Others took notice of the company’s success. On Target was selected to participate in SBIR Investor Initiatives, an NCI-sponsored program that helps SBIR and Small Business Technology Transfer award recipients present their technology to investors and strategic partners.

Catalyzed by NCI’s Investor Initiatives contacts, On Target received $40 million in private financing. Those partnerships opened the door to more investors and eventually garnered the company enough support to launch clinical trials testing CYTALUX during surgeries to remove tumors in people with lung and ovarian cancers.

A shining return on investment

Surgeons were impressed. In those clinical trials, they saw the borders of tumors in real time, cutting out the cancer while preserving as much of the unaffected organ tissue as possible. They even removed cancers that they would have missed without CYTALUX because the tumors were not visible on scans.

In late 2021, the Food and Drug Administration (FDA) approved CYTALUX as an optical imaging agent for adults with ovarian cancer. Approval for adults with lung cancer followed a year later.

Almost 10 years after its first SBIR grant, On Target officially launched CYTALUX, making it commercially available in September 2023. It is now the first FDA-approved imaging agent to detect cancers in the lung and ovaries during surgery in real time.

“The [SBIR] grant helped us understand the full potential of what we have with CYTALUX,” said Tim Biro, R.Ph., chief operating officer of On Target, who along with Sumith is one of the longest-serving members of the company. His gratitude for the chance to see the technology get developed and the company grow from three employees to more than 30 is evident. “SBIR support was really important to the company at that early stage.”

If you ask Sumith about the importance of this work, he’d tell you that the return on investment is simple: “a better outcome for patients with cancer and their families.”