Synthesis and evaluation of fluorine-18 labelled compounds for imaging of bacterial infections with pet.

Syntheses of no carrier added (n.c.a.) 6-fluoro-1,4-dihydro-1-cyclopropyl-4-oxo-7-[4-[18F]fluoro-phenacyl-1-piperacinyl]-chinolincarboxylic acid ([18F]COPCA) and n.c.a. 4-[18F]fluoro-benzoyl-ubiquicidin 29-41 ([18F]UBI 29-41) are described. [18F]COPCA was synthesised within 120 min with a radiochemical yield of 9-12%. [18F]UBI 29-41 was synthesised within 150 min with a radiochemical yield of 15-20%. Both compounds had a specific activity of more than 35 GBq/micromol. The biological activity was verified by measuring its binding to Staphylococcus aureus bacteria. Specific binding was found for [18F]UBI 29-41 (12-17%), whereas no specific binding for [18F]COPCA was found.     

Synthesis of [11C]salicylic acid and related compounds and their biodistribution in mice.

For in vivo measurement of the hydroxyl radical (.OH), we synthesized [11C]salicylic acid, [11C]O-acetylsalicylic acid and [11C]2-methoxybenzoic acid by carboxylation of 2-bromomagnesiumanisol using [11C]CO2. The radiochemical yield of [11C]salicylic acid, [11C]O-acetylsalicylic acid and [11C]2-methoxybenzoic acid calculated from trapped [11C]CO2 in a liquid argon cooled stainless tube was 7.3 +/- 1.6, 5.2 and 10.2 +/- 1.7% (decay corrected), respectively. The uptake of 11C tracers by mouse brain was 0.46, 0.32, and 0.46% dose/g tissue, respectively, at 10 min post injection and presented washout patterns thereafter.     

某些金属离子络合物和有机硒化物的合成及其辐射防护作用

报道了某些金属离子络合物和有机硒化物的合成，并在小鼠上初步评价了它们的辐射防护作用。其中天冬氨酸锌（Ｄ－１）、３，５－二异丙基水杨酸（Ｄ－３）及其铜盐（Ｄ－４）和硒硫辛酸（Ｄ－６）对受到致死剂量照射的小鼠具有一定的防护效果，分别提高活存率４０％、２０％、３０％和４０％。硒取代硫辛酸的一个或两个硫原子后，其抗辐射作用明显减弱，毒性增大。对这一类化合物尚难肯定其辐射防护效果，有待进一步研究．     

Synthesis of non-activated 18F-fluorinated aromatic compounds through nucleophilic substitution and decarboxylation reactions

The synthesis of no-carrier-added 3-[¹⁸F]fluoroanisole, 2-[¹⁸F]fluoroanisole, [¹⁸F]fluorobenzene and 4-[¹⁸F]fluoroveratrole are reported. The strategy consists of amino-polyether supported nucleophilic substitution with [¹⁸F]F⁻ on activated nitro aromatic aldehyde precursors followed by decarbonylation using Tris(triphenylphosphine) rhodium (I) chloride. The experimental parameters for this reaction have been studied and optimized with 2-[¹⁸F]fluoro-4-methoxybenzaldehyde and then successfully applied to four other ¹⁸F-fluorinated aromatic aldehydes. The decarbonylation yields obtained were 84 ± 5% (corrected for decay) within 15 min at 150°C in 1,4-dioxan.     

Synthesis of conjugates of polyhedral boron compounds with tumor-seeking molecules for neutron capture therapy

Recent achievements in design and synthesis of boronated acids, amino acids, glycerols as well as conjugates of polyhedral boron hydrides (ortho-carborane, closo-dodecaborate and cobalt bis(dicarbollide)) with natural porphyrins, carbohydrates and nucleosides are described.     

Tumor model studies of 131I-tetracycline and other compounds.

Iodine-131-tetracycline (131I-TET) was prepared by allowing tetracycline hydrochloride to react with radioiodide in acidic methanol (labeling efficiency greater than 85%). This preparation was found to be stable at--4 degrees C for at least 72 hr. Some minimal in vivo breakdown did occur. The 131I-TET, 67Ga, and several 99mTc compounds were studied in a rat hepatoma model. The incorporation of the radiopharmaceuticals into the tumor occurred rapidly, with peak levels at 0.5 and 24 hr after injection for 131I-TET and 67Ga, respectively. The clearnace of the radiopharmaceutical from nonviable tumor was slower than for viable tumor, and by 72 hr after injection the greatest concentration of radioactivity appeared in the nonviable fraction. All normal tissues showed faster clearance than did tumor tissue, regardless of viability. Decreasing the quantity of 131I-TET injected increased the percent of uptake in the nonviable tumor tissue but had no effect on the viable tumor uptake. Of the 99mTc compounds studied, the phosphates developed the highest tumor-to-background ratios. Unfortunately these ratios were not as high as those achieved for 67Ga or 131I-TET.     

Synthesis of 15N-labeled phthalimide.

A new method for preparing 15N-labeled phthalimide from the reaction between phthalic anhydride and 15N-urea (99.34% 15N) in the presence of ortho-xylene is described in this work. Reaction conditions were the mole ratio of phthalic anhydride to 15N-urea (99.34% 15N) of 3-1 at 140 degrees C and under atmospheric pressure. Excessive phthalic anhydride reacted with ethanol for 90 min. The by-product of diethyl phthalate dissolving in ethanol was separated by filtration. The high yield of 96% of 15N-labeled phthalimide was obtained and the purity and abundance was 99.5% and 99.04%, respectively.     

Applications of perfluorinated compounds as contrast agents in computed tomography.

Perfluorohexylbromide, a nonionic and biologically inert radiodense compound, was evaluated as a potential contrast agent. Pulmonary and gastrointestinal administration of the neat liquid form was tested in dogs in conjunction with computed tomographic body scans. Contrast enhancement was demonstrable in one organ, the spleen, within 6 hr of gastrointestinal administration of perfluorohexylbromide.     

Pancreatic scanning using retrograde injection of technetium-99m-labeled compounds.

With increased clinical availability of endoscopic retrograde pancreatography, a method for retrograde injection of radionuclides into the pancreas became available. A dog model was developed to evaluate resolution and toxicity of retrograde imaging prior to human use. Two groups of technetium-99m-labeled compounds were used. The first included ionic carriers--pertechnetate and pyrophosphate--and the second included particulate carriers--sulfur colloid and albumin microspheres. Parenchymal visualization, absorption patterns, and toxicity in dogs were studied. The results suggest that pyrophosphate, sulfur colloid, and albumin microspheres would all be feasible technetium carriers for use in humans.     

Synthesis of 2-deoxy-2[82Br]bromo-d-mannose and related compounds and their biodistributions in mice

The synthesis of 2-deoxy-2-[⁸²Br]bromo-3,4,6-tri-O-acetyl--d-mannopyranosyl chloride (compound 3b) and 2-deoxy-2-[⁸²Br]bromo-d-mannose (compound 4d), and their biodistributions in mice are described. The reaction of 3,4,6-tri-O-acetyl-d-glucal (compound 2) with unlabeled and labeled bromine chloride (compounds 1a and 1b) generated in situ from the oxidation of bromide with N-chlorosuccinimide gave unlabeled and labeled 2-deoxy-2-bromo-3,4,6-tri-O-acetyl--d-mannopyranosyl chloride (compounds 3a and 3b) with a radiochemical yield of 58% (chemical yield, 63%). The hydrolysis of compounds 3a and 3b with 2N HCl gave 2-deoxy-2-bromo-d-mannose (compounds 4a and 4b) with a radiochemical yield of 72%. The biodistribution of compounds 3b and 4b after injection in mice indicated that 2% of the total injected radioactivity rapidly accumulated in the brain, while 6% of the total injected radioactivity accumulated in the heart; however, the radioactivity started to decline in these two organs after 15 min.Visiting scholar from the School of Pharmacy, Shanghai First Medical College, People's Republic of China     

Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: A boron neutron capture therapy study

Abstract

Purpose: The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined.

Materials and methods: Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from ¹⁰B thermal neutron capture.

Results: BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 μg/10⁹ cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 10¹¹ n/cm² thermal neutron fluence yielded a 20–25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and ⁷Li nuclei that deposit energy in densely ionizing radiation tracks.

Conclusion: Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and ⁷Li nuclei generated from ¹⁰B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.     

Synthesis of 2-deoxy-2-[82Br]bromo-D-mannose and related compounds and their biodistributions in mice

The synthesis of 2-deoxy-2-[82Br]bromo-3,4,6-tri-O-acetyl-alpha-D-mannopyranosyl chloride (compound 3b) and 2-deoxy-2-[82Br]bromo-D-mannose (compound 4b), and their biodistributions in mice are described. The reaction of 3,4,6-tri-O-acetyl-D-glucal (compound 2) with unlabeled and labeled bromine chloride (compounds 1a and 1b) generated in situ from the oxidation of bromide with N-chloro-succinimide gave unlabeled and labeled 2-deoxy-2-bromo-3,4,6-tri-O-acetyl-alpha-D-mannopyranosyl chloride (compounds 3a and 3b) with a radiochemical yield of 58% (chemical yield, 63%). The hydrolysis of compounds 3a and 3b with 2N HCl gave 2-deoxy-2-bromo-D-mannose (compounds 4a and 4b) with a radiochemical yield of 72%. The biodistribution of compounds 3b and 4b after injection in mice indicated that 2% of the total injected radioactivity rapidly accumulated in the brain, while 6% of the total injected radioactivity accumulated in the heart; however, the radioactivity started to decline in these two organs after 15 min.     

Bone scanning with 99Tcm compounds in metastasizing mammary carcinoma.

A comparison of three compounds for bone scanning has been carried out in 9 patients with metastatic mammary carcinoma for evaluating their effectiveness. The best results were obtained with 99Tcm diphosphonate. For the other two compounds tested, 99Tcm polyphosphate and 99Tcm pyrophosphate, no difference could be demonstrated.