The application provides fluorescent dyes, which are cyanine dyes that incorporate additional aza moieties in the indolenium heterocycles and/or in the methine chains connecting them. Symmetrical and unsymmetrical chemically reactive azacyanine dyes are described for conjugation, as well as their bioconjugates for in-vitro and in-vivo assays and fluorescence imaging.

Methods, and related compositions, for the improved synthesis of [.sup.18F]DCFPyL are disclosed. Also provided are methods, and related compositions, for the use of [.sup.18F]DCFPyL so produced.

Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use. ##STR00001##

6-[.sup.18F]Fluoro-2-alkoxynicotinoyl substituted Lys-C(O)-Glu derivatives were identified as efficient imaging probes for PSMA expressing tissues in comparison to other known PSMA specific ligands like [.sup.18F]DCFPyL, [.sup.68Ga]HBED-CC-PSMA, [.sup.18F]PSMA-1007 and [Al.sup.18F]HBED-CC-PSMA. Unexpectedly, the 6-[.sup.18F]fluoro-2-alkoxy and 6-[.sup.18F]fluoro-4-alkoxy substituted analogs showed significant differences in accumulation in PSMA expressing prostate tumor cells. Whereas the 2-alkoxy derivative showed cellular uptake values higher than [.sup.18F]DCFPyL, the cellular uptake of the corresponding 4-alkoxy substituted derivative was significantly lower. Furthermore, in vivo PET studies with 2-alkoxy-substituted probes demonstrated excellent visualization of PSMA positive ganglia with extremely high target to background ratio. In contrast, the 4-alkoxy substituted derivatives showed less favorable biodistribution with significantly lower uptake in PSMA positive tissues. Especially, the .sup.18F-labeled 2-methoxy derivate ((2S)-2-({[(1S)-1-carboxy-5-[(6-[.sup.18F]fluoro-2-methoxypyridin-3-yl)formamido]pentyl]carbamoyl}-amino)pentanedioic acid) demonstrated exceptional clinical efficiency in detecting small PCa lesions, including those which could not be visualized with [.sup.68Ga]HBED-CC-PSMA representing currently the gold standard for the diagnosis of recurrent PCa. Furthermore, this probe is easily accessible on a preparative scale in commercially available automated synthesis modules like GE FASTlab and TRACERlab FX N Pro. Consequently, the novel probe is a valuable tool for the visualization of ganglia and reendothelialization as well as for the diagnosis of glioma, neuropathic pain and atherosclerotic plaques.

Among the various aspects of the present disclosure is the provision of a method for detecting neurodegenerative diseases, disorders, or conditions. Briefly, the present disclosure is directed to a non-invasive method for measuring foveal area and thickness, which has been shown to correlate with the detection of biomarkers used in the detection of neurodegenerative diseases such as Alzheimer's disease and clinical dementia.

Provided are imaging agents comprising a compound of Formula (I), or a pharmaceutically acceptable salt thereof, and methods of their use. ##STR00001##

The invention relates to compounds of formula (II) for using in imaging and particularly for the diagnosis of neurodegenerative diseases.

Provided are imaging agents comprising a compound of Formula I, or a pharmaceutically acceptable salt thereof, and methods of their use. ##STR00001##

The present disclosure relates to a method for measuring the intensity of pain and, more particularly, provides a method capable of measuring the intensity of pain by providing a pain template.

A method for producing a radiofluorinated compound having an aromatic or heteroaromatic ring carrying [.sup.18F] fluorine as first substituent, a bonding unit, which can bind to a peptide or peptide mimetic, and a spacer group connected via bond A.sup.1 to the bonding unit and via bond A.sup.2 to the ring, wherein the bonding unit has second substituent(s) OH, CONH, and/or COOH. The steps include (a) providing a precursor having the ring carrying a substituent Y, bonding unit with the second substituent(s), and spacer group, wherein substituent Y is N.sup.+(R.sup.1R.sup.2R.sup.3), NO.sub.2, Cl, Br, F, or I, and R.sup.1, R.sup.2, and R.sup.3 are independently C.sub.1-C.sub.6 alkyl; and (b) reacting the precursor with a [.sup.18F] fluoride anion in the presence of an activation salt to the radiofluorinated compound, which has a cation N.sup.+(R.sup.4R.sup.5R.sup.6R.sup.7) with R.sup.4, R.sup.5, R.sup.6, and R.sup.7 being independently C.sub.1-C.sub.6 alkyl, wherein the substituent Y is replaced by [.sup.18F] fluoride.