The present technology is directed to compounds, intermediates thereof, compositions thereof, medicaments thereof, and methods related to the imaging of mammalian tissue overexpressing PSMA. The compounds are of Formula I

##STR00001##

or a pharmaceutically acceptable salt thereof, wherein one of R.sup.1, R.sup.2, and R.sup.3 is

##STR00002##

and of Formula IV

##STR00003##

or a pharmaceutically acceptable salt thereof.

Aspects generally relate to a temperature responsive polymer, more specifically to a polymer exhibiting an upper critical solution temperature (UCST) in an aqueous solution. In one aspect, a monomer compound includes one or more amide or thioamide groups; one or more ureido or thioureido groups; and one or more ethylenically unsaturated groups. In one aspect, a polymer, such as a homopolymer or a copolymer, is produced by polymerization of the monomer compound. The copolymer is produced by polymerization of the monomer compound and a comonomer, such as a hydrophobic comonomer, a hydrophilic comonomer, a pH responsive comonomer, a light responsive comonomer, and combinations thereof. The polymer exhibits a UCST from about 1° C. to about 100° C. in an aqueous solution at 1 atm.

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.

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.

Improved methods of causing vasodilation in a human subject are disclosed. In one implementation, the human subject is administered a dose of a nitrate salt of arginine, norvaline, or ornithine, wherein the dose of the nitrate salt of the amino acid in moles of the amino acid is less than a molar amount of the amino acid needed to cause vasodilation in the human subject. In another implementation, the human subject is administered a composition comprising a dose of a nitrate salt and an amount of an amino acid, wherein the dose of the nitrate salt in the composition in moles of the nitrate salt is less than a molar amount of the nitrate salt that needs be administered alone in order to induce vasodilation in the human subject. The amino acid in the composition is selected from the group consisting of: arginine, citrulline, creatine, glutamine, leucine, norvaline, and ornithine.

The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of prostate cancer.

The present invention generally relates to the field of radiopharmaceuticals and their use in nuclear medicine as tracers, imaging agents and for the treatment of various disease states of prostate cancer.

Novel efficient, time-saving and reliable radiofluorination procedures for the production of .sup.18F-labelled active esters via nucleophilic substitution of the corresponding onium precursors with .sup.18F.sup.− are described. The active ester including [.sup.18F]F-Py-TFP and [.sup.18F]TFB produced by one of these methods was used to prepare PSMA-specific PET tracers such as [.sup.18F]DCFPyL. The key advantages of these inventive methods are efficiency, short time of preparation and excellent amenability to automation. A pharmaceutical composition containing at least one PSMA-specific PET tracers prepared by the inventive method is useful for positron emission tomography (PET) imaging, especially imaging prostate tumor.

Novel efficient, time-saving and reliable radiofluorination procedures for the production of .sup.18F-labelled active esters via nucleophilic substitution of the corresponding onium precursors with .sup.18F.sup.− are described. The active ester including [.sup.18F]F-Py-TFP and [.sup.18F]TFB produced by one of these methods was used to prepare PSMA-specific PET tracers such as [.sup.18F]DCFPyL. The key advantages of these inventive methods are efficiency, short time of preparation and excellent amenability to automation. A pharmaceutical composition containing at least one PSMA-specific PET tracers prepared by the inventive method is useful for positron emission tomography (PET) imaging, especially imaging prostate tumor.

The invention relates to a process for preparing a diisocyanate of the formula (A)

##STR00001## where R is selected from the group consisting of alkyl, aryl, and combinations thereof, comprising the following process steps in the indicated order; 1) providing an intermediate of the formula (B) with a process using lysine and urea

##STR00002##

and  where R and each R′ are independently selected from the group consisting of alkyl, aryl, and combinations thereof; and 2) thermolytic cleavage of the intermediate of the formula (B), thereby affording the diisocyanate of the formula (A),
and also to the diisocyanate directly prepared therewith.