[11C]Martinostat for HDAC imaging

[11C]Martinostat is a probe for an enzyme family – namely HDAC that has been known to be dysregulated in brain disorders. Currently, the role of the HDACs in relevant disorders in humans is poorly understood. A positron emission tomography (PET) radiotracer for the HDACs that can provide reliable measurements of HDAC density and distribution could be one important means for understanding the many such disorders linked to this group of enzymes.

Unfortunately, there is no PET radiotracer currently available to study HDAC distribution and function in humans. To address this critical need, we are developing radiotracers for positron emission tomography (PET) such as [11C]Martinostat that can provide molecular-level epigenetic information about the human brain.

[11C]Martinostat binds selectively to class-I isoforms of histone deacetylase (HDAC) enzymes, which are ubiquitously, but heterogeneously, expressed in mammalian tissues. Dysfunctions of HDACs have been associated with a large number of human diseases, notably cancer, central nervous system (CNS) disorders and heart failure. Quantification of HDAC density in human tissues may be a biomarker for certain disease.

Our studies in non-human primates and rodents showed that [11C]Martinostat has excellent brain, heart, kidney, pancreas, and spleen uptake with a high percentage of specific binding. The uptake of [11C]Martinostat can be quantified using compartmental modeling and can be blocked in a dose-dependent manner using FDA-approved drugs targeting HDACs.

The I3 is supporting the development of [11C]Martinostat for human studies under the exploratory investigational new drug (IND) mechanism. The I3 has helped review eIND drafts and faciliated communication with the FDA after submission in order to dramatically facilitate the timeline of success.