Developer sees bright future for nuc med imaging agent

Apomate promises tailored cancer therapy

Clinical evaluation is under way for North American Scientific's Apomate, a binding agent that enables programmed cell death to be imaged using standard gamma cameras. The FDA has not yet granted biologic approval, but the company expects to clear that hurdle and bring the product to market by late 2004.

Apomate, which has been in development since 1999, is actually a kit consisting of three components used to prepare technetium-99m-labeled rh-annexin V, a human protein. It is administered intravenously and designed to facilitate in vivo imaging of apoptosis and necrosis.

During apoptosis, which occurs in heart attacks, organ transplant rejection, and cancer treatment, the molecule phosphatidylserine (PS) migrates to the outer surface of the cell. Once there, it becomes a binding target for Apomate. In necrosis, Apomate binds to PS on the inner leaflet of the cell membrane.

"The goal of chemotherapy is to induce apoptosis in tumor cells," said L. Michael Cutrer, president and CEO of the Chatsworth, CA, company. "We've seen in our clinical trials good correlation between the uptake of Apomate and response to chemotherapy. Ultimately, we hope to provide a mechanism that will enable an oncologist to predict after a single dose of chemotherapy whether a patient is going to respond to that therapy."

Clinical trials are evaluating the ability of Apomate to determine the location and extent of damage resulting from heart attacks and transplant rejection, as well as to assess early response--cancer cell death--to cancer treatment. According to Cutrer, phase I trials involving 15 patients in an oncology protocol showed a strong connection between Apomate uptake and "a clinically meaningful response." The company hopes to replicate those results in a considerably larger patient population when phase III trials begin, possibly by the end of summer. Phase II trials are already under way.

"This is a management tool that to date has no equivalent," Cutrer said. "Providing clinicians with a mechanism to quickly identify chemotherapy responders from nonresponders would enable them to make faster and better therapeutic decisions."

Cutrer considers Apomate extremely important to the company's future success. Because its price has not been fixed, he could not accurately identify its market potential. He estimated, however, that 400,000 chemotherapeutic treatments are performed in the U.S. each year--and that Apomate could play a role in every one of them.

Key to the success of Apomate will be the use of gamma cameras rather than PET scanners. PET is more expensive and less available than SPECT, Cutrer said. And SPECT does a good job of visualizing the radionuclide.

"Also, it's not a simple task to fluorinate this protein, although that's something we're looking into," he said.

The product initially will target various types of cancer and will be marketed primarily to medical oncologists. Cutrer is optimistic that sales will be brisk.

"We're very happy with the clinical results so far," he said. "We believe there's blockbuster potential here, and that Apomate can change the way medicine is practiced. To my knowledge, there's nothing out there that can give you molecular imaging of this response process as quickly as this radiolabeled protein."