The business of ferrying tumor killing particles and depositing them on their targets has been a major part of nanotechnology research. Much of this work focuses on the particles themselves, exploring new ways for them to attack cancer cells, while antibodies do the work of transporting and navigating. Researchers at University of Alabama at Birmingham are investigating direct radioactive “nuking” of cells with lead-212 attached to tumor seeking antibodies.
Radioisotope lead-212 has a half-life of about eleven hours, and in the experiment it was attached to the commonly used Herceptin (trastuzumab) antibody used in cancer treatment that interferes with the HER2 receptor. HER2 is a protein often found in large quantities in breast cancers, so the system essentially delivers the already used cancer therapy along with radioactive lead to the target. The researchers are currently conducting a phase I clinical trial testing the safety of the technique. Initial results on the first three patients are being presented at the Society of Nuclear Medicine and Molecular Imaging annual meeting in Vancouver, Canada.
With an average half-life of 6.7 days, beta emitters looked to be more useful at first. They remained radioactive long enough to be shipped and introduced into patients. They passed through thousand cells before coming to a halt, suggesting they could kill many cancer cells inside large tumors. On the downside, they came with sustained, off-target radiation exposure that dramatically limited their safe dose.
The field had long discussed using alpha emitters instead because they strike nearby cells with greater power, have shorter half-lives for less off-target exposure and penetrate just a few cells before coming to a halt. Unfortunately, the first alpha emitters identified had inappropriate half-lives and were tricky and expensive to produce.
Enter study sponsor AREVA Med, the company that built a system for consistent delivery of pure radium-224 that decays into lead-212 in the time it takes to ship it to any hospital in the world (about 36 hours). Lead-212 is not an alpha emitter, but decays into bismuth-212 which emits alpha particles and then becomes inert within an hour of being introduced to the body. According to the data so far, this spares bone marrow, organs and normal cells.AREVA Med asked UAB to undertake the current study because of Meredith’s clinical trial expertise within the UAB cancer center.
The trial was open to all patients with HER-2 positive cancer, but seven out of the first eight patients happened to have ovarian cancer. All patients underwent extra rounds of imaging to ensure that the radioactivity stayed in the abdomen, close to where metastases occur around primary gastric and ovarian tumors. Researchers watched for signs of long-term toxicity for six months after treatment, but found none. Patients in the study had failed on previous therapies.
UAB: Early data from first human study suggests radiation-antibody combination is safe…
Link: AREVA Med…