Acute cerebral stroke is the most prevalent neurological disorder. Patients with suspected stroke symptoms - but inconclusive imaging - often present a challenge for diagnosis, particularly in differentiating a suspected stroke from non-stroke events, such as transient ischemic attack.
The ability to visualize tissue damage, involving a continued process of cell death in the damaged brain regions, may answer important unmet clinical needs in stroke management. These may include clinical decision making at the sub-acute phase, optimizing use of rehabilitation and real-time evaluation of novel neuro-protective therapies.
[18F]-ML-10 was successfully evaluated in a phase II clinical trial for imaging cell death in patients with acute cerebral ischemic stroke.
Traumatic Brain Injury (TBI)
Traumatic Brain Injury is a major cause of mortality and morbidity among the young population, and it is a difficult condition to diagnose. The trauma leads to accumulation of harmful mediators, causing both primary and secondary damage. Current imaging technology is useful in identifying hemorrhagic regions but cannot diagnose actual damage to brain tissue. [18F]-ML-10 may be useful in addressing this issue.
Shown below is a fluorescence-labeled Aposense® molecular probe used to detect cell death in a pre-clinical TBI study in mice. Twenty-four hours following the injury, a distinct uptake of the probe was detected selectively in the injured brain regions (left), which correlated on cell-by-cell basis with activated caspase staining (right).
J Neurotrauma;25(6):569-80 (2008)
* ApoTrace is an Aposense pre-clinical diagnostic kit distributed by Sigma-Aldrich
Multiple sclerosis (MS) is a chronic, autoimmune condition in which the immune system attacks the central nervous system. There are about 400,000 patients suffering from MS in North America today, with the peak of onset occurring between the ages of 20 and 30. Diagnosis increasingly involves the use of MRI, with gadolinium contrast enhancement for detection of blood-brain barrier disruptions, which are indicative of active MS lesions. However, there are growing concerns about the safety of gadolinium, due to its potential association with nephrogenic systemic fibrosis (NSF), particularly following multiple exposures. Since MS is a chronic disease usually diagnosed at a young age, patients are likely to be exposed multiple times in the course of their disease, creating a need for a gadolinium-free agent for detecting the MS plaques.
Apoptosis plays an important role in the damage occurring in the neurovascular system of MS patients. ML-10 was evaluated in an Experimental Autoimmune Encephalomyelitis (EAE) model for multiple sclerosis, both at the onset of clinical symptoms and at the end-stage of the disease. Increased uptake (2.5-fold above the uptake in healthy mice) of tritium-labeled ML-10 was detected already at the onset of clinical symptoms, and a high uptake level was maintained at the end-stage of the disease. ML-10 offers an opportunity for a gadolinium-free alternative for imaging active MS lesions.
[18F]-ML-10 is an investigational agent, not yet approved for use outside clinical trials