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ABSTRACT: OBJECTIVE: Although radiotherapy is an important treatment strategy for head and neck cancers, it induces tumor repopulation which adversely affects therapeutic outcome. In this regard, fractionated radiotherapy is widely applied to prevent tumor repopulation. Evaluation of tumor proliferative activity using (18)F-fluorothymidine (FLT), a noninvasive marker of tumor proliferation, may be useful for determining the optimal timing of and dose in the repetitive irradiation. Thus, to assess the potentials of FLT, we evaluated the sequential changes in intratumoral proliferative activity in head and neck cancer xenografts (FaDu) using FLT. METHODS: FaDu tumor xenografts were established in nude mice and assigned to control and two radiation-treated groups (10 and 20 Gy). Tumor volume was measured daily. (3)H-FLT was injected intravenously 2 h before killing. Mice were killed 6, 24, 48 h, and 7 days after the radiation treatment. Intratumoral (3)H-FLT level was visually and quantitatively assessed by autoradiography. Ki-67 immunohistochemistry (IHC) was performed. RESULTS: In radiation-treated mice, the tumor growth was significantly suppressed compared with the control group, but the tumor volume in these mice gradually increased with time. In the visual assessment, intratumoral (3)H-FLT level diffusely decreased 6 h after the radiation treatment and then gradually increased with time, whereas no apparent changes were observed in Ki-67 IHC. Six hours after the radiation treatment at 10 and 20 Gy, the intratumoral (3)H-FLT level markedly decreased to 45 and 40 % of the control, respectively (P < 0.0001 vs control), and then gradually increased with time. In each radiation-treated group, the (3)H-FLT levels at 48 h and on day 7 were significantly higher than that at 6 h. The intratumoral (3)H-FLT levels in both treated groups were 68 and 60 % at 24 h (P < 0.001), 71 and 77 % at 48 h (P < 0.001), and 83 and 81 % on day 7 (P = NS) compared with the control group. CONCLUSION: Intratumoral FLT uptake level markedly decreased at 6 h and then gradually increased with time. Sequential evaluation of intratumoral proliferative activity using FLT can be beneficial for determining the optimal timing of and dose in repetitive irradiation of head and neck cancer.
Annals of Nuclear Medicine 02/2013; · 1.50 Impact Factor
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ABSTRACT: Accurate imaging to identify hypoxic regions in tumors is key for radiotherapy planning. [F-18]‑fluoro-misonidazole ([F-18]-FMISO) is widely used for tumor hypoxia imaging and has the potential to optimize radiotherapy planning. However, the biological characteristics of intratumoral [F-18]-FMISO distribution have not yet been fully investigated. In hypoxic cells, the hypoxia-inducible factor-1 (HIF-1) target proteins that induce cellular proliferation and glucose metabolism, glucose transporter-1 (Glut-1) and hexokinase-II (HK-II), are upregulated. In this study, we determined the intratumoral distribution of [F-18]-FMISO by autoradiography (ARG) and compared it with pimonidazole uptake, expression of Glut-1, tumor proliferative activity (Ki-67 index) and glucose metabolism ([C-14]2-fluoro-2-deoxy-D-glucose uptake; [C-14]-FDG) in a glioma rat model. Five C6 glioma‑bearing rats were injected with [F-18]-FMISO and [C-14]-FDG. After 90 min, the rats were injected with pimonidazole and 60 min later, the rats were sacrificed and tumor tissues were sectioned into slices. The adjacent slices were used for ARG and immunohistochemical (IHC) analyses of pimonidazole, Glut-1 and Ki-67. [F-18]-FMISO ARG images were divided into regions of high [F-18]-FMISO uptake (FMISO+) and low [F-18]-FMISO uptake (FMISO-). Pimonidazole and Glut-1 expression levels, Ki-67 index and [C-14]-FDG distribution were evaluated in the regions of interest (ROIs) placed on FMISO+ and FMISO-. [F-18]-FMISO distribution was generally consistent with pimonidazole distribution. The percentage of positively stained areas (% positive) of Glut-1 in FMISO+ was significantly higher compared to FMISO- (24±8% in FMISO+ and 9±4% in FMISO-; P<0.05). There were no significant differences in Ki-67 index and [C-14]-FDG uptake between FMISO+ and FMISO- (for Ki-67, 10±5% in FMISO+ and 12±5% in FMISO-, P = ns; for [C-14]-FDG, 1.4±0.3% ID̸g̸kg in FMISO+ and 1.3±0.3% ID̸g̸kg in FMISO-, P = ns). Intratumoral [F-18]-FMISO distribution reflected tumor hypoxia and expression of the hypoxia‑related gene product Glut-1; it did not, however, reflect tumor proliferation or glucose metabolism. Our findings help elucidate the biological characteristics of intratumoral [F-18]-FMISO distribution that are relevant to radiotherapy planning.
International Journal of Oncology 01/2013; · 2.40 Impact Factor
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ABSTRACT: The mechanistic dissociation of 'tumor starvation' versus 'vascular normalization' following anti-angiogenic therapy is a subject of intense controversy in the field of experimental research. In addition, accurately evaluating changes of the tumor microenvironment after anti-angiogenic therapy is important for optimizing treatment strategy. Sorafenib has considerable anti-angiogenic effects that lead to tumor starvation and induce tumor hypoxia in the highly vascularized renal cell carcinoma (RCC) xenografts. 18F-fluoromisonidazole (18F‑FMISO) is a proven hypoxia imaging probe. Thus, to clarify early changes in the tumor microenvironment following anti-angiogenic therapy and whether 18F-FMISO imaging can detect those changes, we evaluated early changes in the tumor microenvironment after sorafenib treatment in an RCC xenograft by sequential histological analysis and 18F-FMISO autoradiography (ARG). A human RCC xenograft (A498) was established in nude mice, for histological studies and ARG, and further assigned to the control and sorafenib-treated groups (80 mg/kg, per os). Mice were sacrificed on Days 1, 2, 3 and 7 in the histological study, and on Days 3 and 7 in ARG after sorafenib treatment. Tumor volume was measured every day. 18F-FMISO and pimonidazole were injected intravenously 4 and 2 h before sacrifice, respectively. Tumor sections were stained with hematoxylin and eosin and immunohistochemically with pimonidazole and CD31. Intratumoral 18F-FMISO distribution was quantified in ARG. Tumor volume did not significantly change on Day 7 after sorafenib treatment. In the histological study, hypoxic fraction significantly increased on Day 2, mean vessel density significantly decreased on Day 1 and necrosis area significantly increased on Day 2 after sorafenib treatment. Intratumoral 18F-FMISO distribution significantly increased on Days 3 (10.2-fold, p<0.01) and 7 (4.1-fold, p<0.01) after sorafenib treatment. The sequential histological evaluation of the tumor microenvironment clarified tumor starvation in A498 xenografts treated with sorafenib. 18F-FMISO hypoxia imaging confirmed the tumor starvation. 18F-FMISO PET may contribute to determine an optimum treatment protocol after anti-angiogenic therapy.
International Journal of Oncology 09/2012; 41(5):1593-600. · 2.40 Impact Factor
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ABSTRACT: Type 1 diabetes mellitus is characterized by a significant deficit in pancreatic β-cell mass, presumably caused by β-cell apoptosis. We investigated the incidence of β-cell apoptosis in streptozotocin-treated mice and nonobese diabetic (NOD) mice with (99m)Tc-annexin A5.
Vehicle-treated mice, streptozotocin-treated mice, and NOD mice at the ages of 5, 9, 16, and 20 wk (5-8 mice per group) were injected with (99m)Tc-annexin A5 and sacrificed 6 h later for autoradiography, and the regional (99m)Tc-annexin A5 level in the pancreas was evaluated. Pancreatic islets were identified by insulin immunohistochemical staining, and apoptotic cells were determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The (99m)Tc-annexin A5 level in pancreatic islets was expressed as the percentage injected dose per area of pancreatic islets and normalized by animal body weight (%ID × 10(6)/mm(2)/kg). The level of apoptotic cells in pancreatic islets was expressed as the number of TUNEL-positive cells per area of pancreatic islets (cells/mm(2)).
The (99m)Tc-annexin A5 accumulation level was significantly higher (2.5 ± 0.7 vs. 0.7 ± 0.1 %ID × 10(6)/mm(2)/kg, P < 0.05) and the number of TUNEL-positive cells was significantly higher (1,170 ± 535 vs. 5 ± 6 cells/mm(2), P < 0.05) in the pancreatic islets of the streptozotocin-treated mice than in those of the vehicle-treated mice. The (99m)Tc-annexin A5 accumulation level was significantly higher (1.1 ± 0.4 vs. 0.5 ± 0.1 %ID × 10(6)/mm(2)/kg, P < 0.05) and the number of TUNEL-positive cells was significantly higher (152 ± 82 vs. 4 ± 9 cells/mm(2), P < 0.05) in the pancreatic islets of 16-wk-old NOD mice than in those of 5-wk-old NOD mice. In addition, the level of (99m)Tc-annexin A5 correlated with the number of TUNEL-positive cells in the pancreatic islets of the streptozotocin-treated mice (r = 0.821, P < 0.001) and NOD mice (r = 0.721, P < 0.001).
There is significant islet cell apoptosis with (99m)Tc-annexin A5 accumulation in the pancreas of both streptozotocin and NOD mice.
Journal of Nuclear Medicine 08/2012; 53(10):1585-91. · 6.38 Impact Factor
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ABSTRACT: Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes.
Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of (123)I-GLP-1 or (123)I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using (125)I-GLP-1 or (125)I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured.
In the noninvasive imaging studies, a relatively high accumulation level of (123)I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of (123)I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of (123)I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using (125)I-labeled peptides. The AUC of (125)I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1.
This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals.
Annals of Nuclear Medicine 12/2011; 26(2):184-91. · 1.50 Impact Factor
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ABSTRACT: We have developed a radiolabeled uracil derivative, 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU) as a novel single photon emission computed tomography probe for thymidine phosphorylase (TP). This radioiodinated IIMU has a high affinity for TP and highly accumulates in the TP-expressing tumor cell line A431 (human epidermoid carcinoma). To evaluate the specificity of the cellular uptake of IIMU to TP expression, we examined the effects of TP knockdown on the uptake of ¹²⁵I-labeled IIMU (¹²⁵I-IIMU) in the tumor cells.
TP-specific small interfering RNA (siRNA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-specific siRNA (positive control), and negative control siRNA were transfected into A431 cells, respectively. Target-mRNA and protein expression levels of TP and GAPDH were examined 48 and 72 h after transfection, respectively. The cellular uptake level of ¹²⁵I-IIMU was also evaluated 72 h after transfection. The results were compared after normalization with the corresponding negative controls.
After TP-specific and GAPDH-specific siRNA transfection, the expression levels of TP and GAPDH mRNA decreased significantly to 41 and 29%, respectively, compared with the negative control (P<0.001 for both). The expression levels of TP and GAPDH protein also significantly decreased to 34 and 30%, respectively (P<0.001 for both). After TP-specific siRNA transfection, the cellular uptake level of ¹²⁵I-IIMU decreased significantly to 66% (P<0.001). In contrast, GAPDH siRNA transfection did not significantly affect the cellular uptake level of ¹²⁵I-IIMU.
siRNA-mediated TP knockdown significantly decreased the cellular uptake level of ¹²⁵I-IIMU. This finding indicates that the uptake of IIMU in tumor cells is TP specific and directly corresponds to TP expression levels.
Nuclear Medicine Communications 09/2011; 32(12):1211-5. · 1.40 Impact Factor
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ABSTRACT: We evaluated whether the dynamic profile of L-(11)C-methionine (11C-MET) may have an additional value in differentiating malignant tumors from granulomas in experimental rat models by small animal positron emission tomography (PET).
Rhodococcus aurantiacus and allogenic rat C6 glioma cells were inoculated, respectively, into the right and left calf muscles to generate a rat model bearing both granulomas and tumors (n=6). Ten days after the inoculations, dynamic 11C-MET PET was performed by small animal PET up to 120 min after injection of 11C-MET. The next day, after overnight fasting, the rats were injected with 18F-2-deoxy-2-fluoro-D-glucose (18F-FDG), and dynamic 18F-FDG PET was performed up to 180 min. The time-activity curves, static images, and mean standardized uptake value (SUV) in the lesions were calculated.
11C-MET uptake in the granuloma showed a slow exponential clearance after an initial distribution, while the uptake in the tumor gradually increased with time. The dynamic pattern of 11C-MET uptake in the granuloma was significantly different from that in the tumor (p<0.001). In the static analysis of 11C-MET, visual assessment and SUV analysis could not differentiate the tumor from the granuloma in all cases, although the mean SUV in the granuloma (1.48±0.09) was significantly lower than that in the tumor (1.72±0.18, p<0.01). The dynamic patterns, static images, and mean SUVs of 18F-FDG in the granuloma were similar to those in the tumor (p=NS).
Dynamic 11C-MET PET has an additional value for differentiating malignant tumors from granulomatous lesions, which deserves further elucidation in clinical settings.
European Journal of Nuclear Medicine 07/2011; 38(10):1876-86. · 4.53 Impact Factor
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ABSTRACT: We investigated whether 18F-fluorothymidine-positron-emission tomography/computed tomography (18F-FLT-PET/CT) is useful for the evaluation of the very early response to anti-epidermal growth factor receptor (EGFR) antibody cetuximab therapy in human lung cancer xenografts. A human tumor xenograft model was established with a human non-small cell lung cancer cell line. The mice were randomly assigned to four groups: tumor growth follow-up, ex vivo study, PET/CT imaging and non-treated control. Mice were administered saline as control or cetuximab on day 1. An immunohistochemical study with Ki-67 was performed. Tumor volume treated with cetuximab was kept significantly smaller than control after day 8, although there was no difference on day 3. On day 3, 18F-FLT distribution was higher in the tumor than in other tissues, and was significantly decreased by treatment with cetuximab. On PET/CT imaging, 18F-FLT distribution in the tumor was clearly visualized, and the maximum standardized uptake value (SUV) was significantly decreased after treatment with cetuximab (p<0.01). Ki-67 expression was also significantly decreased on day 3 (p=0.01). These results suggest that 18F-FLT-PET/CT can be a useful predictor to determine the response to molecular targeted drugs such as cetuximab at an earlier time point than the change of tumor size.
Oncology Reports 06/2011; 26(3):725-30. · 1.84 Impact Factor
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ABSTRACT: We investigated the performance of the Inveon small-animal PET/SPECT/CT system and compared the imaging capabilities of the SPECT and PET components.
For SPECT, the energy resolution, tomographic spatial resolution and system sensitivity were evaluated with a (99m)Tc solution using a single pinhole collimator. For PET, the spatial resolution, absolute sensitivity, scatter fraction and peak noise equivalent count were evaluated. Phantoms and a normal rat were scanned to compare the imaging capabilities of SPECT and PET.
The SPECT spatial resolution was 0.84 mm full-width at half-maximum (FWHM) at a radius of rotation of 25 mm using a 0.5-mm pinhole aperture collimator, while the PET spatial resolution was 1.63 mm FWHM at the centre. The SPECT system sensitivity at a radius of rotation of 25 mm was 35.3 cps/MBq (4 × 10(-3)%) using the 0.5-mm pinhole aperture, while the PET absolute sensitivity was 3.2% for 350-650 keV and 3.432 ns. Accordingly, the volume sensitivity of PET was three orders of magnitude higher than that of SPECT.
This integrated PET/SPECT/CT system showed high performance with excellent spatial resolution for SPECT and sensitivity for PET. Based on the tracer availability and system performance, SPECT and PET have complementary roles in multimodality small-animal imaging.
European Journal of Nuclear Medicine 12/2010; 38(4):742-52. · 4.53 Impact Factor
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ABSTRACT: The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis, tumor invasiveness and activation of antitumor agents. We evaluated radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ([(125)I]IIMU) having high TP-inhibitory potency as the new radiotracer for SPECT targeting of TP expression in tumors.
The characteristics of the radioiodinated TP inhibitor IIMU were determined by evaluating the uptake by tumor cells in vitro and by biodistribution studies in vivo. The distribution of the radiotracer and the extent of TP-specific uptake by tumors were evaluated by a counting method in tumor-bearing mice.
The in vitro uptake of radiolabeled IIMU by A431 cells along with high TP expressions was attributed to the binding of the radiotracer to its target enzyme, i.e., TP. In vivo distribution of the radiotracer in A431 tumor-bearing mice revealed tumor/blood and tumor/muscle activity uptake ratios of 36 and 106, respectively, at 3 h after the radiotracer injection. On using low TP-expressing tumors and TP blocking studies as controls, minor TP-specific accumulation of the radiotracer was detected in these studies.
According to the binding of radioiodinated IIMU to the angiogenic enzyme TP, it can be concluded that radioiodinated IIMU might be suitable as a SPECT tracer for tumor imaging.
Nuclear Medicine and Biology 05/2010; 37(4):427-32. · 3.02 Impact Factor
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ABSTRACT: Photolysis of 6-chloro-1,3-dimethyluracil and mesitylene in the presence of trifluoroacetic acid (TFA) at low temperature gave 1,3,5,7,9- and 1,3,6,8,10-pentamethylcyclooctapyrimidine-2,4-diones (1b,1c). Sequential photoreaction of the former (1b) resulted in the formation of 9,11-diazapentacyclo[6.4.0.01,3.02,5.04,8]dodecane-2,4-dione (2b) by way of 9-exo-methylene derivative (7b) and cyclobutaquinazoline (8b). On the other hand, UV-irradiation of 1c led to the bond shift isomer (5c) whose photolysis in the presence of TFA gave rise to the formation of the [6.4.0.01,3.02,6.04,8]dodecane isomer (3c).
Photochemistry and Photobiology 04/2007; 74(3):385 - 390. · 2.41 Impact Factor
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ABSTRACT: In order to facilitate the use of the PET-based Strauss test for 5-FU sensitivity, a rapid and facile synthesis of [2-11C]5-fluorouracil ([2-11C]5-FU), based on = [11C]phosgene ([11C]COCl2), is reported.
The key intermediate (E)-beta- benzoylamino-Alpha-fluoroacrylamide (1) and [11C]phosgene was submitted to cyclocondensation to give [2-11C]5-fluorouracil.
[2-11C]5-Fluorouracil was synthesized in 17 min with high (25%) radiochemical yield.
The present study provides a rapid, simple, and efficient synthesis of [2-11C]5-FU, that would serve as a useful prognostic PET tracer for 5-FU chemotherapy.
Journal of pharmacy & pharmaceutical sciences: a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques 02/2007; 10(2):212-6. · 1.65 Impact Factor
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Ken-ichi Nishijima
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ABSTRACT: Positron Emission Tomography (PET) is an advanced non-invasive technology used in the field of nuclear medicine for clinical diagnosis using radiotracers labeled with short-lived positron emitting radionuclides such as (11)C (half-life: 20.4 min), (13)N, (15)O and (18)F. The present study describes an efficient rapid synthesis method for [(11)C]Phosgene ([(11)C]COCl(2)) which is an important potential precursor for preparation of PET radiopharmaceuticals. Catalytic oxidation of [(11)C]CCl(4) using Fe(2)O(3) powder mixed with Fe granules as an oxidizing agent was newly accomplished with a development of fully automated synthetic apparatus. Utilization of produced [(11)C]COCl(2) provided a substantial synthesis of [2-(11)C]thymine as a key intermediate for preparation of [2-(11)C]thymidine, a PET tracer to evaluate cellular proliferation. Direct ring closure reaction of the alkali metal salt of beta-(N-benzoyl-amino)methacrylamide with [(11)C]COCl(2) readily proceeded under mild conditions to afford [2-(11)C]thymine in fair yield reproducibly. By way of further application, a useful PET ligand for beta-adrenoreceptors, S-(-)-[(11)C]CGP-12177 (CGP) was synthesized in markedly high yield with high specific activity and radiochemical purity. CGP for intravenous injection was prepared in 25 min after EOB with a yield of 1.5+/-0.2 GBq. These results of quality control tests demonstrated that CGP preparation is suitable for routine clinical use. Thus, CGP-PET study has been newly added to clinical PET for cardiac functional investigation in Hokkaido University Hospital.
Yakugaku zasshi journal of the Pharmaceutical Society of Japan 10/2006; 126(9):737-45. · 0.39 Impact Factor
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ABSTRACT: Upon UV-irradiation in the presence of piperylene, 5-fluoro-1,3-dimethyluracil (5-FDMU) couples with naphthalenes having either an electron-withdrawing group or an electron-donating group by way of 1,2-cycloaddition via mode selectivity to give the corresponding naphthocyclobutapyrimidines regio- and stereo-selectively.
CHEMICAL & PHARMACEUTICAL BULLETIN 03/2005; 53(2):258-9. · 1.59 Impact Factor
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ChemInform 05/2004; 35(18):no - no.
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ABSTRACT: The reuse of [18O] water after being purified by distillation has been reported to give lower [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) yields, probably due to the presence of organic impurities. In our routine production of [18F]FDG, however, we observed increased [18F]FDG yields with recycled [18O]water. Thus, factors affecting [18F]FDG yield were examined using as-purchased (virgin) and recycled (by photochemical combustion and distillation) [18O]water. [18F]FDG was synthesized by nucleophilic 18F-fluorination on a quaternary 4-aminopyridinium resin. The recycled [18O]water gave an [18F]FDG yield significantly higher than did the virgin water, without any significant difference in the [18F]fluoride yield. Levels of several ionic impurities including Cl- and Ca2+ were significantly higher in the virgin [18O]water than in the recycled water, while significantly larger amounts of organic impurities were detected in the former. Hence, trace amounts of organic impurities were not responsible for the lower [18F]FDG yield. Chloride anion in the [18O]water may compete with [18F]fluoride to lower the [18F]FDG yield.
Applied Radiation and Isotopes 08/2002; 57(1):43-9. · 1.17 Impact Factor
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ABSTRACT: [11C]Phosgene ([11C]COCl2), a useful precursor for labeling several radiopharmaceuticals, is generally produced by catalytic oxidation of [11C]carbon tetrachloride over Fe granules, although in low yields or with poor reproducibility. In order to develop am improved synthesis of [11C]phosgene, two oxidizing agents, Fe2O3 and CuO, were examined. The yield of [11C]phosgene was significantly increased using Fe2O3 powder mixed with Fe granules, while the use of CuO alone, or CuO powder mixed with Fe granules resulted in an insignificant yield. The yield and specific activity of S- (-) [11C]CGP-12177 synthesized using Fe2O3 powder mixed with Fe granules were markedly higher than those synthesized by the previous methods using Fe granules alone or Fe granules mixed with Fe powder. Thus, in the present study, we developed a simple and practical method for the synthesis of [11C]phosgene, which provided an improved yield of S- (-) [11C]CGP-12177.
Nuclear Medicine and Biology 05/2002; 29(3):345-50. · 3.02 Impact Factor
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ABSTRACT: To clarify the contribution of glial cells to octanoate uptake into the brain, we determined the effects of fluoroacetate, a selective inhibitor of glial metabolism, on in vitro brain uptake of [1-14C]octanoate, using rat brain slices. The [1-14C]octanoate uptake significantly decreased, depending on the concentration of fluoroacetate (p = 0.001). The [1-14C]octanoate uptakes at 5 mM (0.23 +/- 0.05% uptake/mg slice) and 25 mM fluoroacetate (0.12 +/- 0.01% uptake/mg slice) were significantly lower than that at control (0.29 +/- 0.02% uptake/mg slice, p < 0.05 and p < 0.001, respectively). The results demonstrate the contribution of glial cells to octanoate uptake into the brain. The potential of [1-11C]octanoate as a PET tracer for studying glial functions is suggested.
Nuclear Medicine and Biology 04/2002; 29(3):303-6. · 3.02 Impact Factor
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ABSTRACT: [18F]FDG was produced by solid-phase 18F-fluorination (resin method) and chemical impurities were determined in the [18F]FDG preparations by ion chromatography. The major chemical impurities were D-glucose (90.5 +/- 6.4 microg/mL), 2-chloro-2-deoxy-D-glucose (11.8 +/- 2.7 microg/mL), and D-mannose (1.7 +/- 0.7 microg/mL), which were expected to be present by considering the synthetic routes. An FDG mass (0.5 +/- 0.2 microg/mL) was also detected in the preparations. No notable radiochemical impurities, including 2-[18F]fluoro-2-deoxy-D-mannose, were detected in the [18F]FDG preparations. Thus, the levels of several chemical impurities were determined in the [18F]FDG preparations produced by solid-phase 18F-fluorination.
Nuclear Medicine and Biology 03/2002; 29(2):275-9. · 3.02 Impact Factor
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ABSTRACT: Background: S-(−)[11C]CGP-12177 is reported to be a useful PET ligand for β-adrenoreceptor in the heart and lung. Its pharmacokinetic properties, however, have not been fully examined due to difficulty in S-(−)[11C]CGP-12177 production. Recently, we have developed a simple and improved synthesis of S-(−)[11C]CGP-12177 with high yields and high specific activity. The aim of this study is to determine pharmacokinetic properties of high specific activity S-(−)[11C]CGP-12177 in vitro and in vivo using rats. Methods: In vitro studies: S-(−)[11C]CGP-12177 (final concentration, 1 nM) with various concentrations of (±)CGP-12177, (±)propranolol, or (−)timolol was added in vitro to rat myocardial slices (n=4 in each condition). Incubation was performed at 30 °C for 90 min. The radioactivity in the myocardial slices was determined at the end of incubation. In vivo studies: Control and (±)propranolol-pretreated (7 μmol/kg, i.v., 5 min prior to S-(−)[11C]CGP-12177 injection) rats (n=4 in each group) were given S-(−)[11C]CGP-12177 (0.4 nmol/kg) intravenously. Radioactivity in tissues was measured at 20 min after injection of S-(−)[11C]CGP-12177. Results: In vitro studies: Uptake of S-(−)[11C]CGP-12177 in the myocardial slices was significantly decreased, depending on the concentration of the β-adrenoreceptor antagonists. S-(−)[11C]CGP-12177 uptake was 26%, 31%, and 36% of the control value, respectively, at 5×10−6 M (±)CGP-12177, (±)propranolol, and (−)timolol. In vivo studies: In the control group, uptake of S-(−)[11C]CGP-12177 was highest in the lung (10.3±0.5% ID/g), followed in decreasing order by the heart (2.4±0.1 %ID/g), kidneys, and liver. Pretreatment with (±)propranolol significantly reduced S-(−)[11C]CGP-12177 uptake in the lung and heart, to 11% and 17% of the control value, respectively (p<0.0001 for both tissues). Conclusions: The accumulation of S-(−)[11C]CGP-12177 in the heart and lung can be largely ascribed to the specific binding of the compound to β-adrenoreceptors, providing further evidence for the feasibility of high specific activity S-(−)[11C]CGP-12177 as an imaging agent for β-adrenoreceptors.
International Congress Series 1264:261-266.
