Abstract: The present invention involves a rapid synthesis of .sup.18 F-FMISO and analogs thereof. New precursors such as 1-(2'-nitro-1'-imidazolyl)-2-0-acetyl-3-0-tosylpropanol, glycerol-1,3-ditosylate-2-0-acetylate, 1-(2'-nitro-1'-imidazolyl)-2,3-0-diacetyl-4-0-tosylbutanol and threitol 1,4-di-tosylate-2,3-0-diacetylate, are also important aspects of the invention.A further aspect of the invention is the development of a hydrophilic PET ligand to image tumor hypoxia. Erythrotosyl analogue of 2-nitroimidazone (Ts-ETNIM) was prepared from a mixture of 2-nitromidazole, ditosylthreitol and cesium carbonate at 60.degree. C. for 1 hr. Ts-ETNIM was isolated at 70% yield. ?.sup.18 F!fluoroerythronitroimidazole (FETNIM) was then prepared from Ts-ETNIM and K.sup.18 F/kryptofix.RTM.. The yield for ?.sup.18 F!FETNIM was 26-30% (60 min, decay corrected). Results of biodistribution and PET studies indicate that ?.sup.18 F!FETNIM has the potential to detect tumor hypoxia and is indicated to be less neurotoxic.

Abstract: The present invention involves a rapid synthesis of .sup.18 F-FMISO and analogs thereof. New precursors such as 1-(2'-nitro-1'-imidazolyl)-2-0-acetyl-3-0-tosylpropanol, glycerol-1,3-ditosylate-2-0-acetylate, 1-(2'-nitro-1'-imidazolyl)-2,3-0-diacetylate, are also important aspects of the invention.A further aspect of the invention is the development of a hydrophilic PET ligand to image tumor hypoxia. Erythrotosyl analogue of 2-nitroimidazone (Ts-ETNIM) was prepared from a mixture of 2-nitromidazole, ditosylthreitol and cesium carbonate at 60.degree. C. for 1 hr. Ts-ETNIM was isolated at 70% yield. ?.sup.18 F!fluoroerythronitroimidazole (FETNIM) when prepared from Ts-ETNIM and K.sup.18 F/kryptofix.RTM.. The yield for ?.sup.18 F!FETNIM was 26-30% (60 min, decay corrected). Results of biodistribution and PET studies indicate that ?.sup.18 F!FETNIM has the potential to detect tumor hypoxia and is indicated to be less neurotoxic.

Abstract: The present invention provides a method for chemically modifying non-ionic, water soluble particulate contrast agents so that they degrade in vivo to their non-ionic parent contrast material and carbon dioxide. According to the present invention, known particulate, non-ionic contrast agents are chemically modified to form a precursor or "prodrug" comprising cyclic carbonates and carbamates of the parent compound. The resulting cyclic carbonates and carbamates are lipid soluble, biodegradable, and can be prepared in large quantities using well-established methods. These cyclic carbonates and carbamates can be converted to particulate contrast media using simple, well known techniques, such as solvent-extraction or solvent evaporation.

Abstract: Applicants describe the synthesis of fluorotamoxifen and iodotamoxifen analogs with the halogen atom positioned on the aliphatic chain of the tamoxifen molecule. The halogenated-tamoxifen derivatives possess superior binding affinities to estrogen receptors of pig uteri compared with tamoxifen. The fluorinated tamoxifens have potential use in imaging estrogen receptors by PET whereas the iodinated tamoxifens have potential use in imaging estrogen receptors by SPECT. Rapid and efficient methods of preparing fluorotamoxifen and iodotamoxifen derivatives with high specific activity are also disclosed. Fluorotamoxifen and iodotamoxifen derivatives may advantageously be used as anti-cancer therapeutic agents to halt estrogen-receptor positive tumors.

Abstract: The synthesis of tamoxifen derivatives, most particularly halo, haloalkyl and hydroxy tamoxifen derivatives, wherein the native tamoxifen molecule includes a substituted chemical group positioned on the aliphatic chain of the tamoxifen molecule, is provided. Methods for imaging estrogen receptors using the tamoxifen derivatives of the invention are also described. The aliphatic chain substituted tamoxifen derivatives of the invention possess greater estrogen receptor binding affinities and more potent tumor cell inhibiting activity than native tamoxifen or tamoxifen derivatives substituted at other locations on the molecule (i.e., non-aliphatic chain substituted tamoxifen, phenolic-ring substituted tamoxifen). Examples of the halogenated tamoxifen derivatives of the invention include chloro-, bromo-, iodo- and fluoro-tamoxifen derivatives, and their corresponding lower alkyl halogenated forms.