The present disclosure relates to chimeric small molecules, which find utility as modifiers of target substrates according to the formula A-L.sub.1-E-B or A-L.sub.1-E-L.sub.2-B, wherein A is a kinase binding moiety; B is a target binding moiety; L.sub.1 and L.sub.2 are each a linker; and E is an electrophilic reactive group. Molecules according to the present invention find use making substrate modifications such as post-translational modifications to targets that are not the natural substrate of the kinase; accordingly, diseases or disorders may be treated or prevented with molecules of the present disclosure.

To provide a compound having high TB and a contrast agent for optical imaging. The compound has a molecular weight of a specific range, the compound in which two polyethylene glycols are bonded to a specific cyanine pigment through a linker. The present invention provides a compound which has a high T/B and which can be used as a contrast agent capable of imaging a tumor portion with high contrast.

Carbamate and beta-amino acid urea-based scaffolds that have high binding affinity to PSMA are disclosed. These scaffolds can be radiolabeled and used for imaging cells and tumors that express PSMA or for cancer radiotherapy. These compounds also can comprise a fluorescent dye and be used for imaging cells and tumors that express PSMA or for photodynamic therapy.

A method for measuring a glomerular filtration rate in a mammalian kidney comprises a source of reporter and marker fluorescent molecules. The fluorescent molecules are introduced into the blood stream of a mammalian subject. Over a period of time, a measurement of the intensities of the reporter and marker fluorescent molecules is taken. A ratio is calculated to determine the health of the subject's kidney. This method measures volume of plasma distribution based on a fluorescence of a marker molecule relative to a fluorescence of a reporter molecule.

The present invention provides a compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof:

##STR00001##

wherein: R.sub.1 and R.sub.2 are each separately selected from the group consisting of hydrogen, alkyl, alkenyl, acyl, and hydroxyalkyl; R.sub.3 is hydrogen or halogen; ring A is a benzene ring or a pyridine ring; ring B is selected from the group consisting of the following formulas (i), (ii), (iii), and (iv):

##STR00002## in the formula (ii), Ra is alkyl; R.sub.4 and R.sub.5 are each separately selected from the group consisting of hydrogen, hydroxy, alkoxy, haloalkoxy, halohydroxyalkoxy, and aminoalkyl; and

##STR00003##

represents a double bond or a triple bond. The above compound can be used as a molecular probe for imaging tau proteins that accumulate in the brain.

Labels and methods are provided for detecting deposits, including drusen, sub-retinal deposits, basal laminar and linear deposits, and the like. The labels can detect the presence, progression, or regression of hydroxyapatite, which can be indicative of the presence or the potential to develop such deposits. The labels can include a conjugate comprising a hydroxyapatite binding moiety and a label moiety, which can provide a detectable signal upon binding of the conjugate to hydroxyapatite. The labels and methods can be utilized to detect deposits in eye tissue, such as the retina, brain tissue, or the like. Methods are also provided for utilizing the present labels to predict or diagnose a neurodegenerative disease, including age-related macular degeneration. Accordingly, some methods can predict or diagnose age-related macular degeneration, including early signs or advanced forms thereof, based on the presence of hydroxyapatite in a tissue sample obtained from a subject.

The present disclosure relates to prostate specific membrane antigen (PSMA) targeted compounds conjugated to near-infra red (NIR) dyes and methods for their therapeutic and diagnostic use. More specifically, this disclosure provides compounds and methods for diagnosing and treating diseases associated with cells and/or vasculature expressing prostate specific membrane antigen (PSMA), such as prostate cancer and related diseases. The disclosure further describes methods and compositions for making and using the compounds, methods incorporating the compounds, and kits incorporating the compounds.

Methods and devices for delivering an agent to a solid tissue in vivo for assessment of efficacy are described. One method involves withdrawing of a needle from and injecting of the agent into the solid tissue; another method involves delivering the agent using a plurality of microdialysis probes to a solid tissue.

The present invention provides a compound represented by the following formula (I), a pharmaceutically acceptable salt thereof, or a solvate thereof: ##STR00001##
wherein: R.sub.1 and R.sub.2 are each separately selected from the group consisting of hydrogen, alkyl, alkenyl, acyl, and hydroxyalkyl; R.sub.3 is hydrogen or halogen; ring A is a benzene ring or a pyridine ring; ring B is selected from the group consisting of the following formulas (i), (ii), (iii), and (iv): ##STR00002## in the formula (ii), R.sub.a is alkyl; R.sub.4 and R.sub.5 are each separately selected from the group consisting of hydrogen, hydroxy, alkoxy, haloalkoxy, halohydroxyalkoxy, and aminoalkyl; and ##STR00003##
represents a double bond or a triple bond. The above compound can be used as a molecular probe for imaging tau proteins that accumulate in the brain.

The invention relates to novel tricarbocyanine-cyclodextrin(s) conjugates useful as markers in the diagnosis of kidney diseases, diagnostic compositions comprising the conjugates, their use, and their production.