International Journal of Radiation Applications and Instrumentation. Part B. Nuclear Medicine and Biology最新文献

11,17β-Dihydroxy-6-methyl-17α -(3-[¹⁸F]fluoro-prop-1 -ynyl)androsta-1,4,6-trien-3-one ([¹⁸F]RU 52461), an ¹⁸F-analog of RU 28362, was synthesized by bromide displacement with [¹⁸F]fluoride in 12–30% overall radiochemical yield (decay-corrected) within 140 min from end of bombardment (EOB). The specific activity was 900–1500 mCi/μmol (33.3–55.5 GBq/μmol) at the end of synthesis (EOS). Biodistribution studies indicated high adrenal and pituitary retention, and uniformly low uptake of [¹⁸F]RU 52461 in all other brain regions of the rat. Except for the pituitary, no specific receptor-mediated uptake of [¹⁸F]RU 52461 could be demonstrated using saturating doses of unlabeled RU 52461 in rat brain. While no change was observed throughout the brain areas in adrenalectomized rats and in animals coinjected with dexamethasone, when compared to controls. PET studies revealed extremely low levels of radioactivity in baboon brain. Therefore, [¹⁸F]RU 52461 does not appear to cross the blood-brain barrier, suggesting that this radiopharmaceutical is not suitable to visualize the brain glucocorticoid binding sites by PET.

Carbon-11-labeled estradiol and hexestrol derivatives were prepared via the reaction of [¹¹Cethylchloroformate with the 2- and 4-amino derivatives of estradiol, the 3′-amino derivatives of hexestrol, and the 1-aminophenoxy derivatives of hexestrol and 1-norhexestrol. The corresponding nonradioactive carbamates were prepared for chemical characterization and in vitro receptor binding assays. The positions of the substituents on the parent molecules were selected with a view to minimize interference with the receptor binding process. In spite of this, affinity for the estrogen receptor was strongly impaired for all carbamate derivatives. Likewise, in vivo, the [¹¹C]carbamate analogs failed to localize in receptor rich tissue via an estrogen receptor mediated process.

In this study, 2-[¹⁸F]fluoro-2-deoxy-d-glucose, ([¹⁸F]FDG) was used to radiolabel human granulocytes in vitro for possible clinical use by positron emission tomography (PET). Uptake of [¹⁸F]FDG was dependent on the amount of glucose in the labelling medium, e.g. when 1 × 10⁷ granulocytes were incubated with [¹⁸F]FDG containing 15μg/mL glucose 80% of [¹⁸F]FDG was incorporated within 30 min, but in the presence of 1 mg/mL of glucose it was reduced to 2%. Increasing the cell concentration and activating the granulocytes with Streptococcus pneumoniae, opsonized zymosan or phorbol myristate acetate all increased the uptake of [¹⁸F]FDG. Retention of the [¹⁸F]FDG by the cells as [¹⁸F]FDG-6-phosphate was also dependent on the extracellular glucose concentration, 9% was released within 60 min in the absence of glucose, but 27% in the presence of 1 mg/mL glucose.

Aspects of the suitability of various labelled amino acids for measuring their local incorporation into proteins by positron emission tomography, especially radiochemical aspects including choice of radionuclide, position of label and ease of preparation, are discussed.

We have recently described a method for radiolabeling monoclonal antibodies, with metallic radionuclides using a new chelating agent N₂S₃. Using this chelate the monoclonal antibodies Lym-1 and B72.3 were labeled with ¹⁸⁶Re and their biological integrity was evaluated in vitro and in vivo. ¹⁸⁶Re-labeled antibodies using N₂S₄ methodology were found to be stable in human serum and retained their immunoreactivity. Intravenous administration of 0.5 mCi ¹⁸⁶Re-labeled antibodies resulted in partial or complete regression of tumor tissue in mice.

This report critically appraises methods for the synthesis of 6-[¹⁸F]fluoro-l-3,4-dihydroxyphenylalanine (6-FDOPA) that are based on labelling by non-regioselective electrophilic fluorination, regioselective fluorodemetalation or nucleophilic substitution. Recommendations for the standardization of labelling procedures, the optimization of radiochemical yield and the assurance of product quality and safety are given. Studies of the metabolism of 6-FDOPA in vivo are also reviewed to emphasize the importance of the biochemical component of the development of this tracer for positron emission tomography (PET).

[4-¹⁸F]2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol ([4-¹⁸F]fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2′-fluoro-4′-acteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-1,2,4-triazol-l-yl)-2-propanol in 19% yield. A modified Schiemann reaction on this product resulted in [4-¹⁸F]fluconazole with a radiochemical yield of 1.0–2.0% (EOS) within 2 h. [4-¹⁸F]Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of [4-¹⁸F]fluconazole to a relatively uniform distribution of radioactivity in most organs.