Bifunctional chelators in the design and application of radiopharmaceuticals for oncological diseases.

Radiopharmaceuticals constitute diagnostic and therapeutic tools for both clinical and preclinical applications. They are a blend of a tracer moiety that mediates a site specific accumulation and an effector: a radioisotope whose decay enables either molecular imaging or exhibits cytotoxic effects. Radioactive halogens and lanthanides are the most commonly used isotopes for radiopharmaceuticals. Due to their ready availability and the facile labeling metallic radionuclides offer ideal characteristics for applications in nuclear medicine. A stable link between the radionuclide and the carrier molecule is the primary prerequisite for in vivo applications. The radionuclide is selected according to its physical and chemical properties i.e. half-life, the type of decay, the energy emitted and its availability. Bifunctional chelating agents are used to stably link the radiometal to the carrier moiety of the radiopharmaceutical. The design of the bifunctional chelator has to consider the impact of the radiometal chelate on the biological properties of the target-specific pharmaceutical. Here, with an emphasis on oncology, we review applications of radiopharmaceuticals that contain bifunctional chelators, while highlighting successes and identifying the key challenges that need to be addressed for the successful translation of target binding molecules into tracers for molecular imaging and endoradiotherapy.

Somatosensory areas of manatee cerebral cortex: histochemical characterization and functional implications.

A histochemical and cytoarchitectural analysis was completed for the neocortex of the Florida manatee in order to localize primary sensory areas and particularly primary somatosensory cortex (SI). Based on the location of cytochrome oxidase-dense staining in flattened cortex preparations, preliminary functional divisions were assigned for SI with the face represented laterally followed by the flipper, body and tail representations proceeding medially. The neonate exhibited four distinct patches in the frontoparietal cortex (presumptive SI), whereas juvenile and adult specimens demonstrated a distinct pattern in which cytochrome oxidase-dense staining appeared to be blended into one large patch extending dorsomedially. This differential staining between younger versus older more developed animals was also seen on coronal sections stained for cytochrome oxidase, myelin, or Nissl bodies. These were systematically analyzed in order to accurately localize the laminar and cytoarchitectural extent of cytochrome oxidase staining. Overall, SI appears to span seven cytoarchitectural areas to which we have assigned presumptive functional representations based on the relative locations of cytochrome oxidase-dense staining.