The present invention relates to methods of diagnosis and therapy for neurodegenerative diseases and disorders.

A compound of Formula (I) or a pharmaceutically acceptable ester, amide, solvate, or salt thereof, or a salt of such an ester or amide or a solvate of such an ester amide or salt, is disclosed. Compositions comprising the compound and methods of use are also disclosed. Those dimeric Evans Blue derivatives, denoted as N(tEB)2, reversibly bind two molecules of albumin via the two albumin binding regions of each NtEB in the dimer, resulting in significantly increased binding affinity to albumin and extended circulation half-life in vivo. Further, when the N(tEB)2 is conjugated to a peptide therapeutic, the in situ formation of the complex of N(tEB)2 with two albumin molecules resulted in increased resistance of the peptide therapeutic from proteolysis.

##STR00001## ##STR00002## ##STR00003## ##STR00004##

A method of reducing radiation exposure of a non-cancerous tissue of a patient diagnosed with a cancer includes administering to the patient an agent capable of competing for binding sites on a surface of the non-cancerous tissue, provided that the administration is carried out after a waiting period that follows administration of a compound including a radionuclide to the patient, the compound having affinity for both a cancerous tissue and the non-cancerous tissue, and, further provided that the binding sites have an affinity for both the agent and the compound.

Disclosed herein are tetrazines substituted with groups that result in a high click conjugation yield in vivo and high click release yields. In one aspect, the invention relates to kits having the tetrazines and a dienophile, preferably a trans-cyclooctene. In another aspect, the kits of the invention are for use as a medicament.

Provided herein are prodrugs comprising targeting moieties that specifically bind extracellular antigens, enzyme-cleavable linkers, and innate immune system activators. An enzyme-cleavable linker can covalently link a targeting moiety to an innate immune system activator. Also provided are methods of treating cancer, methods of imaging cancer, and methods of monitoring treatment of cancer.

A method of reducing radiation exposure of a non-cancerous tissue of a patient diagnosed with a cancer includes administering to the patient an agent capable of competing for binding sites on a surface of the non-cancerous tissue, provided that the administration is carried out after a waiting period that follows administration of a compound including a radionuclide to the patient, the compound having affinity for both a cancerous tissue and the non-cancerous tissue, and, further provided that the binding sites have an affinity for both the agent and the compound.

Described herein are markers, conjugates, compositions and methods for hypoxia imaging, mapping, and therapy. A compound comprising bio-reductively activated (BA) arm, linker arm and a mapping click wherein BA contains one for more of substituted or unsubstituted 2/4/5-substituted nitroimidazoles, or substituted benzotriazene-1,4-dioxides, or substituted 1,2,3/1,2,4-triazoles, or substituted 1,4-benzoquinones, or a combination of two homo-or hetero BA moieties, wherein linker arm contains C1-16 alkane, alkene, alkyne, alicyclic or aromatic linkers with or without hetero atoms as in ethers, amine, esters, acid, amides, 5 and 6 membered sugar sings with the substitution as described above, both monosaccharides and disaccharides, wherein mapping click contains one of substituted or unsubstituted N3-, CN, SCN, substituted alkynes for click chemistry. Said compound undergoes in situ click reaction after its distribution in cells or tissues to link to a reporting group which may be unchelated or chelated with a metal-radioactive or non-radioactive-, or a radiohalogen for PET/SPECT, or a dye for fluorescent/optical reporting group, thus accomplishing hypoxia imaging

A method of reducing radiation exposure of a non-cancerous tissue of a patient diagnosed with a cancer includes administering to the patient an agent capable of competing for binding sites on a surface of the non-cancerous tissue, provided that the administration is carried out after a waiting period that follows administration of a compound including a radionuclide to the patient, the compound having affinity for both a cancerous tissue and the non-cancerous tissue, and, further provided that the binding sites have an affinity for both the agent and the compound.

Disclosed herein are isotopically labeled calcofluor derivatives and uses of such to detect fungi, such as filamentous fungi, including Aspergillus species, such as by positron emission tomography (PET) scanning. In some examples, the disclosed compounds have a formula of ##STR00001## wherein R.sup.1 is an amine, a hydroxyl group, a sulfide, a carboxylic acid, an amide, an alkyl, or aryl; R.sup.2 is NHC(O)R.sup.3-L or C(O)NHR.sup.3-L, wherein R.sup.3 is an aryl or an aliphatic group (such as alkyl); each R.sup.4 independently may be selected from halogen, aliphatic (such as alkyl), aryl, amine, hydroxyl, haloalkyl, carboxylic acid, amide, aralkyl, cyano, ester, thiol, thioether, or alkoxy; each R.sup.5 independently may be selected from hydrogen, aralkyl, alkyl, or aryl, with any one of the aralkyl, alkyl, or aryl groups optionally being substituted with any one of the substituents provided for R.sup.4; each n independently is 1, 2, 3, 4, or 5; and L is .sup.18F or a chelator capable of chelating a radiolabel (such as chelators for [.sup.18F]AlF, .sup.64Cu, .sup.68Ga), 1,4,7,10-tetraazacyclododecane-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-triacetic acid (NOTA).

Disclosed herein are isotopically labeled calcofluor derivatives and uses of such to detect fungi, such as filamentous fungi, including Aspergillus species, such as by positron emission tomography (PET) scanning. In some examples, the disclosed compounds have a formula of

##STR00001##

wherein R.sup.1 is an amine, a hydroxyl group, a sulfide, a carboxylic acid, an amide, an alkyl, or aryl; R.sup.2 is NHC(O)R.sup.3-L or C(O)NHR.sup.3-L, wherein R.sup.3 is an aryl or an aliphatic group (such as alkyl); each R.sup.4 independently may be selected from halogen, aliphatic (such as alkyl), aryl, amine, hydroxyl, haloalkyl, carboxylic acid, amide, aralkyl, cyano, ester, thiol, thioether, or alkoxy; each R.sup.5 independently may be selected from hydrogen, aralkyl, alkyl, or aryl, with any one of the aralkyl, alkyl, or aryl groups optionally being substituted with any one of the substituents provided for R.sup.4; each n independently is 1, 2, 3, 4, or 5; and L is .sup.18F or a chelator capable of chelating a radiolabel (such as chelators for [.sup.18F]AlF, .sup.64Cu, .sup.68Ga), 1,4,7,10-tetraazacyclododecane-tetraacetic acid (DOTA) or 1,4,7-triazacyclononane-triacetic acid (NOTA).