Radiohalogenated α-amino acids are a diverse and useful class tumor imaging agents suitable for positron emission tomography and single photon emission computed tomography. These tracers target the increased rates of amino acid transport exhibited by many tumor cells. The most established clinical use for radiolabeled amino acids is imaging primary and recurrent gliomas, and there is growing evidence that they may also be useful for other oncologic applications, including neuroendocrine tumors and prostate cancer. This review focuses on the synthesis, radiolabeling, and preclinical evaluation of three series of nonnatural radiohalogenated amino acids: alicyclic, α,α-dialkyl, and 1H-[1,2,3]triazole amino acids which target system L, system A, and cationic amino acid transport systems, respectively.

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A series of reboxetine analogs was synthesized and evaluated for in vitro binding as racemic mixtures. The best candidate (INER) was synthesized as the optically pure (S,S) enantiomer, labeled with iodine-123 and its in vivo binding determined by SPECT imaging in baboons. The in vivo specificity, selectivity and kinetics of [ 123 I]INER make it a promising agent for imaging NET in vivo by noninvasive SPECT imaging.The norepinephrine transporter (NET) is a protein with twelve transmembrane-spanning domains, located at the pre-synaptic terminal of noradrenergic neurons. The principal physiological function of NET is to removes excess norepinephrine (NE) from the synaptic cleft to terminate the action of NE (avoiding over-stimulation) and to recycle NE into the presynaptic neuron (active reuptake) for later re-release. Brain structures known to be rich in NET include the locus coerulus, (brainstem area); thalamus, hippocampus and throughout the cerebral cortex, whereas low densities are found in cerebellum and striatum. 4 NET has been implicated in the pathophysiology of numerous neuropsychiatric and neurodegenerative disorders, including depression (reduced level of NE in the synapse appears to down-regulate the level of NET), 5,6 arousal, 7 anxiety, 8,9 attention-deficit/hyperactivity disorder (atomoxetine 1 is the first non-stimulant selective NET inhibitor for the treatment of ADHD 10 ), 11 and Alzheimer's disease. 12 Therefore, the development of a specific radioligand to quantify the variation of NET density in vivo will be of great utility as a diagnostic tool to better understand the etiology and pathogenesis of these neuropsychiatric disorders, as well as a tool to evaluated potential new drugs targeting the NET.

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The novel PET radioligand 11C-N,N-dimethyl-2-(2′-amino-4′-hydroxymethylphenylthio)benzylamine (11C-HOMADAM) binds with high affinity and selectively to the serotonin transporter (SERT). The purpose of this study was to develop a reliable kinetic model to describe the uptake of 11C-HOMADAM in the healthy human brain. Methods Eight volunteers participated in the study; 5 of them were fitted with arterial catheters for blood sampling and all were scanned on a high-resolution research tomograph after the injection of 11C-HOMADAM. Regional distribution volumes and binding potentials were calculated with 2- and 4-parameter arterial-input compartment models, a 3-parameter reference tissue compartment model, and the Logan graphic approach. Results The 2-parameter arterial-input compartment model was statistically superior to the 4-parameter model and described all brain regions. Calculated binding potentials agreed well between the arterial-input model and the reference tissue model when the cerebellum was used as the reference tissue. The Logan graphic approach was not able to estimate the higher concentration of SERT in the dorsal raphe than in the midbrain. Conclusion 11C-HOMADAM is a highly promising radioligand with high ratios of specific binding to nonspecific binding in known SERT-rich structures, such as the raphe nuclei. The 3-parameter reference tissue model approach permits a simplified quantitatively accurate method for estimating SERT binding potentials.