The high in vivo stability of 2,2-dihydroxymethyl-3-[ 18 F]fluoropropyl-2-nitroimidazole ([ 18 F]DiFA) prompted us to evaluate neopentyl as a scaffold to prepare a radiotheranostic system with radioiodine and astatine. Three DiFA analogues with one, two, or without a hydroxyl group were synthesized. While all 125 I-labeled compounds remained stable against nucleophilic substitution, only a 125 I-labeled neopentyl glycol was stable against cytochrome P450 (CYP)-mediated metabolism and showed high stability against in vivo deiodination. 211 At-labeled neopentyl glycol also remained stable against both nucleophilic substitution and CYP-mediated metabolism. 211 At-labeled neopentyl glycol showed the biodistribution profiles similar to those of its radioiodinated counterpart in contrast to the 125 I/ 211 At-labeled benzoate pair. The urine analyses confirmed that 211 Atlabeled neopentyl glycol was excreted in the urine as a glucuronide conjugate with the absence of free [ 211 At]At − . These findings indicate that neopentyl glycol would constitute a promising scaffold to prepare a radiotheranostic system with radioiodine and 211 At.
We found that acetonitrile acted as a reactant under the conventional reaction conditions for aliphatic nucleophilic 18 Ffluorination in acetonitrile to provide the N-alkyl 3-aminobut-2enenitrile as one of the side products. Dimerization of acetonitrile promoted by a complex of K 2 CO 3 and K222 provided 3-aminobut-2-enenitrile, which acted as nucleophile to provide N-alkyl amino derivatives. Based on the finding, avoiding acetonitrile in the drying of [ 18 F]fluoride as well as 18 Flabeling enabled the preparation of 18 F-labeled compounds containing only a small amount of the corresponding alcohol. Finally, we used an automated synthesizer to achieve an efficient phase-tag-assisted synthesis of 18 F-labeled stilbene derivative as a 18 F-labeled amyloid-β ligand.
DNA damage in the irradiated cells. The present investigation was carried out to evaluate the radiobiological effect of 223 Ra in 3 different prostate cell models (PC-3, U-2OS metastatic lines, and normal RWPE) by assays of clonogenic survival and DNA damage. Clonogenic cell survival curves were analyzed for different cell lines after irradiation with 225 kVp X-rays from 0 to 8 Gy (dose rate 0.594 Gy/ min), external a-particles (241 Americium) from 0 to 2 Gy (dose rate 1.579 Gy/ min) and 223 Ra from 0 to 0.5 Gy (dose rate 1.389 mGy/min). The results showed a superior efficacy of 223 Ra in comparison with the external a source in all cell lines but with a cell type dependency. The Relative Biological Effectiveness (RBE) for 50% survival for RWPE is 6.07 and 7.97, for external aparticles and 223 Ra respectively. For U-2OS is 6.36 and 8.9 and finally for PC-3 the values are 3.63 and 7.47. Lastly, the induction and repair of DNA damage by different radiation qualities was analyzed by immunofluorescence (53BP1) for doses up to 2 Gy and recovery times of 1, 4, 24 and 96h. For all irradiation setups there is a linear relationship between the number of foci and the absorbed dose. The level of induction and the shape of the kinetics curves are radiation-and cell-specific with the highest induction of foci observed after X-ray irradiation, the lowest after external a irradiation, and 223 Ra being slightly higher than external a particles. In terms of repair, foci induced by external a source or 223 Ra are repaired approximately 3.5 times slower than the X-ray induced breaks in the same cell line. These observations support the higher propensity for complex DNA-damage induced by heavy particles as reported in the literature. Interestingly, exposure to 223 Ra severely affects the nuclear structure with a significant number of giant nuclei, and a large fraction of cells undergoing mitotic catastrophe, features not seem to the same extent with external beam irradiation. In conclusion, our results suggest that response to Radium-223 is cell-specific and that better effectiveness does not solely depend on the DNA damage complexity. Reference:
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