• Assessment of the change in the uptake of [18F]-ML-10 by the target lesion(s) in response to SRS, as observed by comparing the PET/CT scans before and after SRS. Target lesion is defined as having a minimal diameter of 1.5 cm [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  

• Assessment of the relationship between the change in uptake of [18F]-ML-10 by the metastatic target lesions as observed in the PET/CT scans obtained before and after irradiation, and shrinkage of the metastatic target lesion, as assessed by MRI. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  
• Evaluation of the safety of [18F]-ML-10 when administered for 3 consecutive PET/CT scans to patients with brain metastases undergoing SRS. [ Time Frame: one month ] [ Designated as safety issue: Yes ]
  

Drug: 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10)
[18F]-ML-10 will be administered as an intravenous bolus injection (in 3-10 ml sterile saline solution, containing no more than 10% ethanol by volume). The radiation dose of [18F]-ML-10 administered at each session will be 300-500 MBq (8.1-13.5 mCi) and the mass dose will not exceed 20 µg.
Radiation: Stereotactic Radio-Surgery (SRS) therapy
As a standard of care,patients will be delivered a radiation dose of 18-24 Gy to each target lesion.
Procedure: Positron Emission Tomography
Up to 3 sessions of brain PET/CT, pre-treatment, early post-treatment and late post-treatment. Each session will include one day in which a single [18F]-ML-10 injection will be given, followed by one PET/ CT session, comprising up to three scans, within 220 minutes after tracer administration (two half lives of 18F).

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.