Evaluation of the Efficacy and Safety of [18F]-ML-10, as a PET Imaging Radiotracer, in Early Detection of Response of Brain Metastases of Solid Tumors to Radiation Therapy.

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 proposed indication for which [18F]-ML-10 is
being developed is for early assessment of response of solid tumors to radiation and
chemoradiation 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.

Additional Phase 2 study demonstrated the suitability and safety of 18F-ML-10, designed to
serve as a PET radiotracer for early detection of cellular apoptosis of brain metastases in
response to WBRT. The relationship between the early change in 18F-ML-10 uptake by the
tumor, observed during or upon completion of treatment, and subsequent tumor shrinkage as
observed by MRI eight weeks after the completion of WBRT, was demonstrated.18F-ML-10
demonstrated a good safety profile with no drug-related AEs or any effect on safety
parameters.

Inclusion Criteria:

1. Male or female patients with metastatic non- hematological solid tumors, with one or
more brain metastases, of which at least one lesion has a diameter ≥1.5 cm, as
confirmed by anatomical imaging (GBCA-enhanced MRI), wherein this lesion (or lesions)
is scheduled to be treated by SRS.

2. ECOG performance status of 0, 1 or 2 at the time of enrollment.

3. Women of child-bearing potential must have a negative blood pregnancy test at
screening and use an adequate and medically acceptable contraceptive method.

4. Willing and able to follow the protocol requirements.

5. Able to provide written informed consent.

Exclusion Criteria:

1. Unstable medical condition, such as ischemic heart disease, or any other disease or
medical condition that may place the patient at added risk during the study, as
assessed by the Principal Investigator. A patient with a seizure disorder, focal or
generalized, not adequately controlled by anti-convulsant therapy, and /or patient
who have experienced an event of focal or generalized seizure within 7 days prior to
screening will be considered neurologically unstable.

2. Any indication of a risk for an imminent brain herniation, as evaluated by the
Principal Investigator, based on the findings on brain MRI.

3. Treatment with whole brain radiation therapy (WBRT) within 3 months prior to
screening.

4. Evidence for hemorrhage within any of the brain metastases.

5. Any known psychiatric disorder other than mild depression or anxiety that may affect
adherence to the study requirements.

6. Known allergy to gadolinium.

7. Any contraindication to MR imaging (e.g., metal implant, aneurysm clip, pacemaker).

8. Other condition that, in the opinion of the Investigator, might jeopardize the safety
of the patient, or the adequate evaluation of study results.

9. Treatment with any investigational drug, device or biologic agent within 30 days
prior to administration of [18F]-ML-10.