This FOA is intended to stimulate the development of radioligands for molecular targets (e.g., receptors, cell adhesion molecules, intracellular messengers, and disease related proteins) that are of broad interest to the scientific community. The widespread availability and use of these radioligands are expected to: 1) accelerate research on identifying and characterizing the neural circuits and pathways implicated in the pathophysiology of brain disorders (especially mental and behavioral disorders, substance abuse, neurodegenerative disorders, and pediatric brain disorders) and brain changes with age, and 2) facilitate the identification of new therapeutic targets and the development of new compounds as potential therapeutic agents. Research partnerships among investigators in both academia and pharmaceutical and biotechnology industries are encouraged to more rapidly develop PET and SPECT radiotracers and apply neuroimaging in drug discovery, biomarker development//qualification, and pathophysiological studies.

Molecular targets for which radioligands (agonist and antagonist ) are needed include, but are not limited to, the following. Please contact program staff to determine program priorities and molecular targets of interest to specific NIH Institutes or refer to the Internet addresses listed above for each of the participating NIH Institutes.

• Receptors: adenosine; adrenergic: alpha 1, alpha 2; cannabinoid: CB1, CB2; corticotropin releasing hormone: CRF R1, CRF R2; dopamine: D1, D3, D4, D5; estrogen; GABA A subunits; GABA ion channel; GABA B; glutamatergic, glycine site; metabotropic glutamate subtypes; muscarinic subunits; neurokinin receptors: NK1, NK2, NK3; neuronal nicotinic receptor subunits: alpha 7 & alpha 4 beta 2; NMDA subunits; opioid receptors: mu, delta, kappa; serotonin: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2C, 5-HT5, 5-HT6, 5-HT7; voltage gated ion channels: Ca, Na, K - M current proteins.
• Transporters: vesicular ACh; GABA; glutamate; glycine; glutamine; NET; VMAT, excitatory amino acid transporters.
• Markers for glia ,glial activation, and glial cell death.
• Enzymes: choline acetyltransferase; dopamine beta-hydroxylase; GABA transaminase; glutamic acid decarboxylase; glutaminergic; phosphodiesterases; tyrosine hydroxylase.
• Intracellular targets: abnormal proteins or protein aggregates including synuclein, prion protein, amyloid or tau deposition; diacylglycerol; gene expression/transcription markers; markers of neurogenesis or neuronal cell death; markers of mitochondrial function; lipid metabolism; neuroinflammatory markers: cytokines, COX inhibitors; peptidases; phosphatases; phospholipases; protein kinases; stem cells.

See full description in NIH Guide: R21 PA-06-461; R33 PA-06-462; R21/R33 PA-06-463