Society of Nuclear Medicine 2009: Alpha-Particle-Emitting Radiopeptide Produces Tumor Response
TORONTO, ONTARIO, June 23, 2009 — Data from a preclinical study presented at the Society of Nuclear Medicine 56th Annual Meeting suggest that α therapy, in association with fast-clearing peptides, can be effective in treating prostate cancer.
The approach that investigators took was to treat tumors with highly specific radiopeptides that bind with tumor cells using specific therapeutic radioactive substances that emit α particles, which are attached to the radiopeptide.
In a 3-group study using a prostate cancer mouse model, Damian Wild, MD, currently a resident in nuclear medicine at the University College of London, United Kingdom, et al in the Division of Radiological Chemistry at the University Hospital Basel in Switzerland, injected 1 group of mice with 213Bi-DOTA-pepsin (213Bi), which emits α particles. A second group was injected with β-emitting 177Lu-DOTA-pepsin (177Lu), and a third group received no treatment.
Small-volume disease is suitable for α-particle-emitting radiopeptides, according to Dr Wild. When the tumor is very small, α particles are more effective than β particles in irrigating the tumor," he said. "They can even irrigate single cells."
The Swiss team evaluated the maximum tolerated dose, the biodistribution, and the dosimetry of each agent.
The short half-life of 213Bi is not a disadvantage in treating very small tumors, noted Dr Wild. "The accumulation of our tracer in these tumor cells is very fast, less than 30 minutes," he explained.
Indeed, 1 hour after injection of 213Bi or 177Lu, the prostate cancer tumor uptake was 9% IA/g and 11.6% IA/g, respectively (P = .02).
Dr Wild et al found that the maximum tolerated dose of the α-emitting 213Bi and the β-emitting 177Lu were 5 × 5 MBq and 4 × 28 MBq, respectively, corresponding to kidney doses of 6 Gy and 6.7 Gy.
They observed that 213Bi was more effective than 177Lu at the maximum tolerated dose. Specifically, complete remission of cancer was achieved in 70% of mice that were injected with the α-emitting particle, compared with 20% of those injected with the β-emitting particle.
Moreover, survival, defined as more than 30 weeks, was 60% and 20%, respectively, among mice injected with the α-emitting particle and mice injected with the β-emitting particle. Mice that received no treatment did not reach the 30-week survival mark.
Investigators are now recruiting subjects to participate in a phase 1 study aimed at assessing a safe and effective dose of 213Bi that can be administered to patients.
Peter Conti, MD, PhD, a past President of the Society of Nuclear Medicine and a Professor of Radiology and Engineering at the University of Southern California at Los Angeles, noted that the study points to the availability of nonconventional isotopes for nuclear imaging.
"We have to remember that it is preclinical, so there will always be an issue of translation [to humans]," said Dr Conti. "The important thing to remember is that there are other isotopes besides the β-emitters. The α-emitters are potentially useful."
Alpha-emitters are isotopes that emit very high energy. Consequently, more safety precautions have to be taken when working with these isotopes, said Dr Conti. "With the proper handling systems in place, there should be no problems in working with them," he said.
The study is novel in its approach—the radiation is delivered selectively to the tumor site and a solid tumor is being targeted. "When we see developments like this in the arena of solid tumors using therapeutic isotopes, that is important," Dr Conti added.
Source: Medscape Medical News
