18F ML-10 for Early Detection of Response of Brain Metastases to WBRT
The purpose of this study is to evaluate the potential of [18F]-ML-10 to serve as a non-invasive imaging tool for the early detection of apoptosis in brain metastases in response to radiation therapy. Such early detection may improve clinical management of patients with brain metastases, as it may help early identification of non-responders, and subsequently potentially lead to optimization of radiation dose, early decision on focal irradiation of selected, non-responsive lesions, or early referral of the patient to surgery. The experimental design of the present study aims to evaluate the potential of non-invasive PET examination with [18F]-ML-10, to provide the clinician early in the course of treatment, via non-invasive molecular imaging of radiation-induced apoptosis, information on tumor responsiveness, that is currently available only several weeks to months after completion of the radiotherapy.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||An Open-Label Study to Evaluate 18F ML-10 as a PET Imaging Radiotracer for Early Detection of Response of Brain Metastases to Whole Brain Radiation Therapy (WBRT)|
- Assessment of a change in the uptake of [18F]- ML-10 by the tumor as observed in comparing the PET scans before and after WBRT. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Assessment of a relationship between the change in uptake of [18F]- ML-10 by the tumor, observed in the PET scans obtained during the study, and tumor shrinkage in response to treatment, as assessed by MRI or CT according to the RECIST criteria. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Detection of a potential change in the uptake of [18F]- ML-10 by the healthy brain tissue, as observed in comparing the PET/CT scans before and after WBRT, reflecting potential damage to intact brain tissue, as an adverse effect of the irradiation. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Assessment of the correlation between the PET/CT region of interest (ROI), delineated by [18F]-ML-10 imaging, and the corresponding anatomical imaging. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
- Assessment of the safety of [18F]-ML-10 when administered to cancer patients undergoing WBRT. [ Time Frame: one month ] [ Designated as safety issue: Yes ]
|Study Start Date:||March 2008|
|Study Completion Date:||December 2008|
|Primary Completion Date:||December 2008 (Final data collection date for primary outcome measure)|
Experimental: 18F ML-10
Intervention - 18F ML-10 PET/CT imaging for early detection of response of brain metastases to WBRT
Other: 18F ML-10
Patients will undergo 2-3 brain PET/CT sessions; A pre-treatment session and 1-2 sessions post WBRT treatment. Each PET/CT session will be done following intravenous administration of 18F-ML-10, to assess tracer uptake by the tumor.
Other Name: 18F ML-10 PET/CT imaging
Early assessment of the efficacy of anti-cancer therapy is highly desirable and an unmet need in clinical oncology. Currently, treatment efficacy is mostly measured by following tumor size by anatomical imaging (CT scan or MRI). However, changes in tumor size may be observed only after several weeks to several months after completion of treatment. Meanwhile, in cases where there is no response, the patient is unnecessarily exposed to treatment's side effects, and precious time may be lost before the initiation of an alternative, potentially more beneficial line of therapy. Therefore, there is an urgent and serious need for better tools for monitoring of tumor response to anti-cancer treatments.
To address this need, [18F]-ML-10, a novel small molecular-weight probe (MW 205) was developed for clinical detection of apoptosis in vivo by positron emission tomography (PET). [18F]-ML-10 is a member of the ApoSense family of compounds, a novel class of molecular probes for molecular imaging of cell death. The first clinical indication for which [18F]-ML-10 is being developed is imaging of apoptosis in clinical oncology to monitor tumor response to radiation therapy.
Previous preclinical and clinical studies have substantiated the safety of [18F]-ML-10, its very high stability in vivo, its favorable biodistribution profile, and its efficacy in clinical detection of cell death. In preclinical studies, the selective retention of [18F]-ML-10 in the focus of the neurovascular cell death in cerebral ischemia was demonstrated in respective animal models. 18F-ML-10 has been examined in two clinical trials in Uppsala Imanet, Sweden, and has been found safe in administration to healthy subjects and to elderly subjects with acute ischemic cerebral stroke. In these clinical trials, [18F]-ML-10 was also found efficacious in the clinical imaging of apoptosis, being either physiological apoptosis as observed in the testes in young healthy males, and pathological cell death, as observed in the brains of patients with acute ischemic cerebral stroke.