Trial Information

Evaluation of Efficacy and Safety of 18FML10, as a PET Imaging Radiotracer, in Early Detection of Response of Brain Metastases of Non-Hematological 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.