Brain pharmacology of intrathecal antisense oligonucleotides revealed through multimodal imaging.

Intrathecal (IT) delivery and pharmacology of antisense oligonucleotides (ASOs) for the CNS have been successfully developed to treat spinal muscular atrophy. However, ASO pharmacokinetic (PK) and pharmacodynamic (PD) properties remain poorly understood in the IT compartment. We applied multimodal imaging techniques to elucidate the IT PK and PD of unlabeled, radioactively labeled, or fluorescently labeled ASOs targeting ubiquitously expressed or neuron-specific RNAs.

SPECT Imaging of Muscle Injury with [Tc]MDP in a Mouse Model of Muscular Dystrophy.

Purpose: Tc-99m methylene diphosphonate ([Tc]MDP) is an in vivo bone imaging agent that also accumulates in injured skeletal muscle cells. The objective of this study was to investigate if [Tc]MDP could be used to detect muscle injury in the mdx mouse model of Duchenne muscular dystrophy (DMD).

Procedures: Static whole-body single-photon emission computed tomography/computed tomography (CT) scans were acquired at 2 h post-injection of [Tc]MDP in two cohorts of animals at different sites: one cohort of mice at 6, 15, and 19 weeks of age, and a separate cohort at 16 weeks.

Topographical control of multiple cell adhesion molecules for traction force microscopy.

Cellular traction forces are important quantitative measures in cell biology as they have provided much insight into cell behavior in contexts such as cellular migration, differentiation, and disease progression. However, the complex environment in vivo permits application of cell traction forces through multiple types of cell adhesion molecules. Currently available approaches to differentiate traction forces among multiple cell adhesion molecules are limited to specialized approaches to decouple cell-cell from cell-extracellular matrix (ECM) tractions.