June 13, 2011 (San Antonio, Texas) — A novel and highly potent radiopeptide called 213Bi-DOTATOC shows efficacy in targeting neuroendocrine tumors and inducing the remission of metastases without causing severe toxicity, according to preliminary research presented here at the Society for Nuclear Medicine 2011 Annual Meeting.
DOTATOC, which is a tumor-targeting probe labeled with different radionuclides, has been under investigation at the University Hospital of Heidelberg, in Germany, for more than a decade, and mimics the endocrine-system-regulating hormone somatostatin. The latest advance for the treatment is the use of the alpha-emitter 213 bismuth.
Radiotherapies for the treatment of neuroendocrine cancer commonly use beta-emitting particles; however, researchers have been investigating alpha therapy in hard-to-treat cases because of its near-range and high-energy effect when injected.
Because the therapy has exceptionally high cytotoxicity, however, a key focus of the current research is on appropriate dosing, the investigators explain.
To further investigate the alpha-particle emitter, the researchers in Germany administered the therapy to 10 patients with neuroendocrine liver metastases who were not responsive to previous treatment with beta-particle peptide therapy.
The results indicated that the minimal effective dose for inducing partial remission (>30% of the tumor diameter) was 1 GBq 213Bi-DOTATOC.
Importantly, no acute kidney, endocrine, or hematologic toxicity higher than grade 0/1 was observed in the first steps of dosing increases (≤2.5 GBq cumulative activity; ≤1.5 GBq per cycle).
A short-term follow-up demonstrated reduced tumor perfusion (increase in time to peak intensity >25%) in 7 of 9 patients; the morphologic long-term response is pending.
Lead investigator Clemens Kratochwil, MD, said that as the study continues, the number of subjects enrolled in the study who have tolerated the therapy has increased.
"The 213Bi-DOTATOC was given as the last possible treatment option when the patients did not respond to standard therapies, including 90Y- and 177Lu-DOTATOC (beta-particle emitters)," said Dr. Kratochwil, who is from the University of Heidelberg and the Institute for Transuranium Elements, European Commission, Joint Research Centre, in Karlsruhe, Germany.
"Since it was well tolerated by the first patients and showed promising antitumor efficacy, we continued this alpha therapy. The study now includes 14 patients," he said.
"When writing the abstract, the mid-term follow-up (of about 6 months) was only done for the first 9 of 10 patients. Currently, none of the 14 patients who started the new treatment have dropped out or died."
Considering the exceptional cytotoxicity, the results so far are promising. Dr. Kratochwil cautioned that the results are preliminary; there still could be serious risks, and the treatment, for now, is being looked at only for late-stage disease.
"We were surprised by both the low acute toxicity and the relative good response. However, chronic (late) toxicity and, theoretically, induction of secondary cancer can be a problem after exposure to radioactivity."
"Therefore, this treatment should not be used for patients in an earlier stage of disease — at least until more experience is available," he said.
"Next in this research will be the evaluation of late toxicity, and if complications occur in the follow-up, the treatment would have to be stopped," Dr. Kratochwil said.
The tumor-targeting probe used in the therapy — DOTATOC — only targets neuroendocrine tumors, which are relatively rare. If the therapy is successful, additional probes, designed to carry alpha-particle emitters specifically into the cells of other types of cancers, such as prostate cancer, would need to be developed for the treatment of those diseases, Dr. Kratochwil said.
He added that 213Bi is currently only available in very small amounts. However, once its therapeutic efficacy is proven, it might be produced more regularly.
The findings nevertheless offer the promise of a new approach to tackle severe metastatic neuroendocrine tumors, said Michael M. Graham, MD, PhD, professor of radiology and radiation oncology and director of nuclear medicine at the University of Iowa College of Medicine in Iowa City.
"Alpha-emitters are a particularly attractive approach for radiotherapy-injected agents because of their very powerful but short-range radiation," he explained. "The particles are so powerful that just a single alpha particle can kill a cell as it is emitted."
"The alpha particle from bismuth 213 has a remarkably high energy, compared with almost any other particle we deal with; as such, it should be extraordinarily effective."
The findings to date are encouraging and offer hope for a more effective approach to treating the disease, Dr. Graham added.
"The fact that the study showed overall reduced tumor profusion and volume in 7 of the 9 patients, with minimal toxicity, indicates that they can probably go to even higher doses without toxicity. This opens up a different approach to treating some of these tumors that may be effective."
Dr. Kratochwil and Dr. Graham have disclosed no relevant financial relationships.
Society for Nuclear Medicine (SNM) 2011 Annual Meeting. Abstract 29. Presented June 5, 2011.
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Cite this: Novel Radiopeptide Appears to Be 'Extraordinarily Effective' - Medscape - Jun 13, 2011.
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