Insight: Research Edition

Fall 2006

Nuclear Medicine Offering Novel Options for Difficult-to-Treat Cancers

In cancer therapy, there is a fine line between helping a patient and hurting a patient. Many drugs and technologies that can effectively kill cancer cells also cause irreparable harm to the patient, and so have been put on the back shelf. Today, thanks to advances in drug delivery systems and creative thinking, some of those shelved options are giving cancer patients new hope.

Researchers at Colorado State University’s Diagnostic Imaging Group’s Nuclear Medicine Section and the Flint Animal Cancer Center are at the forefront of efforts to develop and test viable cancer treatments using radioactive nucleotides including Indium-111 and samarium. Indium-111 studies are targeted towards cancers that are diffused throughout the body, for example, malignant lymphoma, while the samarium studies are focused on osteosarcoma (bone cancer). Dr. Phillip Steyn is principal investigator on the Indium-111 project, collaborating with colleagues from the Mayo Clinic, and Dr. Nicole Ehrhart is leading the samarium study.

“Bone cancer is commonly diagnosed in pet animals,” said Dr. Ehrhart, an Associate Professor in the Department of Clinical Sciences. “Veterinarians at the Animal Cancer Center diagnose and care for hundreds of new cases of canine osteosarcoma (OSA) every year. Unfortunately, it is a disease that also affects humans, most commonly children.”

Treatment for osteosarcoma consists of surgery to remove the tumor, followed by chemotherapy to delay the spread. Loss of limb and/or function is still a relatively common occurrence for OSA patients, despite the increase in limb salvage procedures performed, and decisions about treatment and amputation can be agonizing for patients, parents and owners. Despite continuing improvements in treatment, approximately 40 percent of children with OSA die of their disease. In dogs, more than 90 percent of patients eventually die of OSA.

“Although radiation therapy is not part of the current standard of care for OSA in people, recent evidence in human patients suggests that radiation improves progression-free interval and quality of life in patients with extremity OSA who have refused surgical therapy or in whom surgery is not possible,” said Dr. Ehrhart, an ACVS board-certified surgeon. “In addition, existing evidence in dogs suggests that the use of radiation in combination with chemotherapy increased tumor kill to clinically favorable levels over either treatment alone. We believe the beneficial role of radiation for treatment of OSA in children and dogs has likely been underestimated. New radiation treatments are available that can minimize radiation effects to normal adjacent tissues, yet provide improved tumor kill over standard OSA treatment.”

Dr. Ehrhart is studying a new method of delivering samarium to avoid dangerous side effects that restrict its potential as a cancer therapy. It involves isolating the circulation to the leg with the tumor from the rest of the body’s circulation by placing the leg on a heart-lung machine. The drug can then be delivered safely to the tumor, without exposing the rest of the body to its potentially toxic effects. The amount of samarium left in the tumor bone isn’t enough to cause the harmful side effects, but because it’s delivered directly to the tumor, it reaches high enough concentrations to kill the tumor. After the drug is delivered to the tumor, the drug is flushed out of the perfusion circuit and the body’s own circulation to the leg takes over again. If successful, veterinary surgeons will make a huge impact on the care of both dogs and children with bone cancer.

Dr. Steyn is taking another approach, looking at more of a Trojan Horse delivery system, for cancers that are difficult to treat because they have spread throughout the system.

“What we have found is that tumor cells, with their high metabolic rate, have an affinity for Vitamin B-12,” said Dr. Steyn. “Vitamin B-12 on its own won’t do any damage, but when we attach radioactive material to it, we are in essence making a smart bomb that can potentially destroy the tumor cell. Labeling with radioactive material basically produces internal radiation as opposed to an accelerator beam, which has an external source, and we hope this approach lessens the damage inflicted on healthy tissue.”

Dr. Steyn’s research team is currently conducting dose escalation studies to evaluate dose efficacy. So far, he notes, the levels of Indium-111 delivered to canine patients have not been shown to kill tumors nor harm the body (the patients go on to receive standard OSA treatment). The project, which is privately funded, will likely expand to look at other labeling candidates that may be effective against other cancer types.

“The exciting part of these research projects in nuclear medicine is that they may offer one more tool for oncologists to reach for when they are devising treatment programs for their patients – and one more tool may make the difference between life and death,” said Dr. Steyn. “I envision that these types of treatments, using radioactive materials, will not stand alone but will be part of a comprehensive treatment program for any given patient, giving them greater hope for a positive outcome.”