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mood disorders) and therefore are conceptualized as more precise treatment targets. These ligands (e.g., [11C]raclopride for D2 receptors, [18F]setoperone for 5-HT2receptors) can be used to measure the occupancy of receptors induced by varying doses of medications, and the degree of occupancy can then be correlated with level of symptom improvement or side effects to determine the level of receptor occupancy required for optimal treatment. This approach is now widely used in order to determine the optimal doses of some psychoactive drugs. The number of available ligands that are U.S. Food and Drug Administration (FDA)-approved is limited, however, and so the development of new and better ligands for drugs of many types continues to be a significant challenge.

For many years [18F]fluorodeoxyglucose-2-deoxy-D-glucose (FDG) has been used to identify the location and size of cancer lesions and to monitor their response to treatment using PET. FDG, while useful, is also relatively crude and nonspecific. The application of imaging technology to monitoring treatment targets can be substantially enhanced if investigators develop new amino acid ligands (tyrosine, methionine, thymidine) that aim at more specific targets, such as hormones (e.g., receptors for estrogen, testosterone) or substrates involved in protein or nucleic acid synthesis.

Novel Technologies to Improve Treatment by Manipulating Intracellular Activity

Most current applications of imaging technology to improving treatment examine activity on a large scale: systems, organs, lesions, etc. A new technology has recently emerged that permits imaging at the intracellular level and the ability to manipulate cellular function. This technology is referred to as “optogenetics” because it uses light-responsive proteins derived from algae (channelrhodopsin and halorhodopsin) that can be used to manipulate neuronal firing by opening or closing ion channels. Channelrhodopsin responds to blue light and produces neuronal firing, while halorhodopsin responds to yellow and silences the cell. Because halorhodopsin also responds to red or near infrared, and because infrared can pass more deeply into tissue, optogenetics offers the possibility of providing nonsurgical control over circuits deeply located in the brain. Optogenetics—a relatively new technology—has been used to study many facets of neuroscience, such as brain reward circuits and mechanisms of memory. It has the potential to supplant deep brain stimulation as a treatment for diseases such

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