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Posted: June 16, 2009
Aposense Imaging Agent Detects Early Cell Death Induced by Radiation in Patients With Brain Metastases
(Nanowerk News) An imaging agent used during PET scans to highlight apoptosis (programmed cell death) appears to help oncologists detect the effect of radiation treatment on brain metastases (tumors from elsewhere in the body that have spread to the brain) early in treatment, according to new data presented today at the 56th Annual Meeting of the Society of Nuclear Medicine, taking place June 13-17 in Toronto, Ontario, Canada.
"Patients with brain metastases have a poor prognosis. The sooner we know if a tumor is responding the more we can help these patients. These results have the potential to radically change the way we as oncologists think about monitoring treatment response," said Aaron Allen, MD, a radiation oncologist at the Davidoff Comprehensive Cancer Center of the Rabin Medical Center, in Petach-Tikva, Israel, and the principal investigator on the trial. "By using this imaging agent known as [18F]-ML-10, we might be able to immediately measure the rate of programmed cell death induced by radiation, and evaluate whether treatment is effective early on, whereas standard imaging only allows us to evaluate treatment two or three months after it was completed."
[18F]-ML-10 (ML-10) is a PET tracer developed by Aposense Ltd., the leading developer of agents targeting apoptosis (programmed cell death) for molecular imaging and therapy.
For the study, physicians administered ML-10 radio-labeled with the radio-isotope 18-F to ten patients with brain metastases and performed a PET scan to determine baseline levels of apoptosis, which occurs spontaneously within the pre-treatment tumor. They administered ML-10 and performed another PET scan on day nine or 10 to identify changes in apoptosis as a result of treatment.
Seven patients completed the study and eight tumors were available for evaluation. All tumors demonstrated at baseline clear images of pre-treatment apoptosis, with ML-10 uptake increasing over time within the tumors as compared to the non-target tissue or blood, confirming selective retention of ML-10 in apoptotic regions of the non-treated tumors, as expected given the known presence of spontaneous tumor apoptosis. Following treatment, the signal to background ratio in irradiated tumors increased over time nearly 2-fold and showed a marked enhancement of the accumulation rate of ML-10.
"We are pleased to see additional evidence that imaging treatment induced cell death with ML-10 may provide physicians early indication of the tumor's response to treatment," said Yoram Ashery, CEO of Aposense. "We look forward to presenting additional follow-up data on the clinical response of these patients soon."
Apoptosis is a genetically controlled program of cell death, inherent in any nucleated cell in the body and therefore often referred to also as "cell suicide." Upon activation, the apoptotic program executes a well-characterized sequence of events by which the cell undergoes fragmentation and elimination by macrophages, without damaging the surrounding tissue. Apoptosis is a universal process of cell death and it plays a role in most medical disorders, making it one of the important processes of cell biology. For example, apoptosis has important roles in oncology, both in the process of tumor growth, as well as in treatment with most therapies which aim to induce death in cancer cells. Targeting cells undergoing apoptosis, for imaging or delivering therapy, can therefore have broad clinical applications.
About Molecular Imaging
Molecular imaging is an emerging field which aims to non-invasively visualize biological processes in vivo. The ability to image disease-related biological processes may allow physicians to detect disease early, characterize the disease better and to personalize treatment by real-time monitoring of therapeutic effect. Molecular imaging depends on special molecules (probes) that can selectively target these biological processes, while carrying an imaging moiety for visualization, such as 18F or other positron emitting radio-isotopes that can be visualized by PET.
Aposense Ltd. is a molecular imaging and drug development company, leading the translation of the science of apoptosis (programmed cell death) into clinical practice. Aposense introduces novel imaging and therapeutic agents based on rationally designed, nano-mechanisms for selective targeting of cells undergoing apoptosis. Aposense technology is based on a new, patented class of small molecular probes that selectively identify and accumulate within apoptotic (dying) cells in vivo. Apoptosis plays a role in many disease areas, including oncology, neurology and cardiology. Aposense probes for Molecular Imaging enables real-time visualization of the biological activity of disease, its onset, change in course and response to therapy, and to personalize treatment for the individual patient in cancer and other diseases. Therapeutic applications of Aposense technology in pre-clinical development include targeted anticancer therapy by using apoptotic cells in tumors as targets for specific delivery and activation of cytotoxic agents in the tumor.