A Study on Preparation of 3'-18FFluoro-3'-deoxythymidine and Its Biodistribution in 9L Glioma Bearing Rats / 핵의학분자영상

PURPOSE: Several radioisotope-labeled thymidine derivatives such as [11C]thymidine was developed to demonstrate cell proliferation in tumor. But it is difficult to track metabolism with [11C]thymidine due to rapid in vivo degradation and its short physical half-life. 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) was reported to have the longer half life of fluorine-18 and the lack of metabolic degradation in vivo. Here, we described the synthesis of the 3'-[18F]fluoro-3'-deoxythymidine ([18F]FLT) and compared with [18F]FET and [18F]FDG in cultured 9L cell and obtained the biodistribution and PET image in 9L tumor bearing rats. MATERIAL AND METHOD: For the synthesis of [18F]FLT, 3-N-tert-butoxycarbonyl-(5'-O-(4,4'-dimethoxytriphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl)-beta-D-threopentofuranosyl)thymine was used as a FLT precursor, on which the tert-butyloxycarbonyl group was introduced to protect N3-position and nitrobenzenesulfonyl group. Radiolabeling of nosyl substitued precursor with 18F was performed in acetonitrile at 120 degrees C and deproteced with 0.5 N HCl. The cell uptake was measured in cultured 9L glioma cell. The biodistribution was evaluated in 9L tumor bearing rats after intravenous injection at 10 min, 30 min, 60 min and 120 min and obtained PET image 60 minutes after injection. RESULTS: The radiochemical yield was about 20-30% and radiochemical purity was more than 95% after HPLC purification. Cellular uptake of [18F]FLT was increased as time elapsed. At 120 min post-injection, the ratios of tumor/blood, tumor/muscle and tumor/brain were 1.61+/-0.34, 1.70+/-0.30 and 9.33+/-2.22, respectively. The 9L tumor was well visualized at 60 min post injection in PET image. CONCLUSION: The uptake of [18F]FLT in tumor was higher than in normal brain and PET image of [18F]FLT was acceptable. These results suggest the possibility of [18F]FLT as an imaging agent for brain tumor.

In vivo targeting of ERGpotassiumchannels inmice and dogs by a positron-emitting analogue of fluoroclofilium

The antiarrhythmic clofilium is an efficient blocker of hERG1 potassium channels that are strongly expressed in the heart. Therefore, derivatives of clofilium that emit positrons might be useful tools for monitoring hERG1 channels in vivo. Fluoroclofilium (F-clofilium) was synthesized and its channel-blocking properties were determined for hERG1 and hEAG1 channels expressed in HEK 293 cells and in Xenopus oocytes. When applied extracellularly in the whole-cell patch-clamp configuration, F-cloflium exhibited a slower onset of block when compared with clofilium, presumably owing to its lower membrane permeability. When applied in the inside-out configuration at the intracellular membrane side, it blocked hEAG1 channels almost as efficiently as clofilium (IC50 1.37 nM and 0.83 nM, respectively). Similar results were obtained for hERG1, showing Fclofilium is a potent hERG1 and hEAG1 channel blocker once it has reached the intracellularly accessible target site at the channel. Using the 18Flabeled analog we studied the in vivo binding and distribution of F-clofilium in mice and a dog. Greatest activity was found in kidneys and bones. A small but significant enrichment of activity in the dog myocardium known for its expression of cERG1 channels allowed to depict the myocardium of a living dog by PET. Thus, F-clofilium is a useful tool for imaging hERG channels in living organisms.

A Study on the Synthesis and Its Biodistribution of C - 11 and F - 18 Labelled Choline / 대한핵의학회잡지

No abstract available.

A Study on the Synthesis , Labeling and Its Biodistribution of Estradiol Derivatives / 대한핵의학회잡지

OBJECTIVES: Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. METHODS: Among the various estradiol derivatives, 17alpha-[123I]iodovinyl estradiol ([123I]IVE) has been prepared from 17alpha-ethynyl estradiol. Labeling of E-17alpha-[123I]iodovinyl estradiol (E-[123I]IVE) was carried out using peracetic acid with [123I]NaI and Z-[123I]IVE labelling was archived using chloamine- T/HCl solution with [123I]NaI. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[123I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. RESULTS: The labeling yield of two isomers was 92% and 94% (E-[123I]IVE and Z-[123I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[123I]IVE). CONCLUSION: These results suggest the possibility of using E-[123I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.

Study for the Synthesis of 123IIdoxifene and Its Uptake in the Breast Cancer Cell / 대한핵의학회잡지

PURPOSE: Idoxifene is currently entering phase II clinical trials for the treatment of advanced breast cancer. The radiolabeled idoxifene using 123I provides an opportunity for clinical pharmacology with single photon emission computed tomography (SPECT). The purpose of this study was to prepare radiolabeled idoxifene using 123I and to determine its cell uptake of breast cancer cell line. MATERIALS AND METHODS: With a view to evaluating new anticancer drugs, we are investigating the novel antiestrogen pyrrolidino- 4-iodotamoxifen (idoxifene). [123I]Idoxifene has been prepared in no-carrier-added form using a tributyl stannylated precursor which has been synthesized by means of (2-chloroethoxy)benzene with (+/-)-2- phenylbutanoic acid on the basis of previously reported standard methods. The biodistribution and dynamic behavior of the compound were investigated using the comparative breast cancer cell line, MCF-7 (estrogen receptor-positive) and MDA-MB-468 (non-estrogen receptor). RESULTS AND CONCLUSION: Acylation of (2-chloroethoxy)benzene with (+/-)-2-phenylbutanoic acid gave the versatile ketone (81%) which reacted with 1,4-diiodobenzene to give triphenylethylene as a mixture of E and Z geometric isomers, which were separated by the recrystallization in ethanol. The E-isomer was treated with pyrrolidine to give idoxifene (67%). In order to incorporate radioactive iodine into the 4-position, the 4-stannylated precursor was prepared (30%). The yield of radioiodination was 90-92% with a high radiochemical purity greater than 98%. The ratio of tumor uptake of the breast cancer cell line between MCF-7 and MDA-MB-468 was about 1.7.

Analysis of Heavy Metals in 201TlTlCl Injection Using Polarography / 대한핵의학회잡지

PURPOSE: Thallous-201 chloride produced at Korea Cancer Center Hospital(KCCH) is used in detecting cardiovascular disease and cancer. Thallium impurity can cause emesis, catharsis and nausea, so the presence of thallium and other metal impurities should be determined. According to USP and KP, their amounts must be less than 2 ppm in thallium and 5 ppm in total. In this study, the detection method of trace amounts of metal impurities in [201Tl]TlCl injection with polarography was optimized without environmental contamination. MATERALS AND METHODS: For the detection of metal impurities, Osteryoung Square Wave Stripping Voltammetry method was used in Bio-Analytical System (BAS) 50W polarograph. The voltammetry was composed of Dropping Mercury Electrode (DME) as a working electrode, Ag/AgCl as a reference electrode and Pt wire as a counter electrode. Square wave stripping method, which makes use of formation and deformation of amalgam, was adopted to determine the metal impurities, and pH 7 phosphate buffer was used as supporting electrolyte. RESULTS: T1, Cu and Pb in thallous-201 chloride solution were detected by scanning from 300 mV to -800 mV. Calibration curves were made by using TlNO3, CuSO4 and Pb(NO3)2 as standard solutions. Tl was confirmed at -450 mV peak potential and Cu at -50 mV. Less than 2 ppm of Tl and Cu was detected and Pb was not detected in KCCH-produced thallous-201 chloride injection. CONCLUSION: Detection limit of thallium and copper is approximately 50 ppb with this method. As a result of this experiment, thallium and other metal impurities in thallous-201 chloride injection, produced at Korea Cancer Center Hospital, are in the regulation of USP and KP. Polarograph could be applied for the determination of metal impurities in the quality control of radiopharmaceuticals conveniently without environmental contamination.

F-18-FDG Whole Body Scan using Gamma Camera equipped with Ultra High Energy Collimator in Cancer Patients: Comparison with FDG Coincidence PET / 대한핵의학회잡지

PURPOSE: The aim of this study is to demonstrate the feasibility of 2-[fluorine-18] fluoro-2-deoxy-D-glucose (F-18-FDG) whole body scan (FDG W/B Scan) using dual-head gamma camera equipped with ultra high energy collimator in patients with various cancers, and compare the RESULTS with those of coincidence imaging. MATERIALS AND METHODS: Phantom studies of planar imaging with ultra high energy and coincidence tomography (FDG CoDe PET) were performed. Fourteen patients with known or suspected maligancy were examined. F-18-FDG whole body scan was performed using dual-head gamma camera with high energy (511 keV) collimators and regional FDG CoDe PET immediately followed it. Radiological, clinical follow up and histologic RESULTS were correlated with F-18-FDG finding. RESULTS: Planar phantom study showed 13.1 mm spatial resolution at 10 cm with a sensitivity of 2638 cpm/MBq/ml. In coincidence PET, spatial resolution was 7.49 mm and sensitivity was 5351 cpm/MBq/ml. Eight out of 14 patients showed hypermetabolic sites in primary or metastatic tumors in FDG CoDe PET. The lesions showing no hypermetabolic uptake of FDG in both methods were all less than 1 cm except one lesion of 2 cm sized metastatic lymph node. The metastatic lymph nodes of positive FDG uptake were more than 1.5 cm in size or conglomerated lesions of lymph nodes less than 1 cm in size. FDG W/B scan showed similar RESULTS but had additional false positive and false negative cases. FDG W/B scan not visualize liver metastasis in one case that showed multiple metastatic sites in FDG CoDe PET. CONCLUSION:S: FDG W/B scan with specially designed collimators depicted some cancers and their metastatic sites, although it had a limitation in image quality compared to that of FDG CoDe PET. This study suggests that F-18-FDG positron imaging using dual-head gamma camera is feasible in oncology and helpful if it should be more available by regional distribution of FDG.

Production of Re-188 / 대한핵의학회잡지

188Re (beta=22 MeV; gamma=155 keV; T1/2=16.9 hours) is an attractive therapeutic radioisotope which is produced from decay of reactor-produced tungsten-188 parent (T1/2=69 days). 188W has been produced from the double neutron capture reaction of 186W. 188Re can be easily obtained by elution of saline on alumina based 186W/188Re generator, which is commercially available. Complexes labelled with 188Re have been developed for the radiotherapy treatment of diseases because of the desirable nuclear properties of the radioisotope and it's chemical properties similar to those of technetium, a well established diagnostic agent.

Biodistribution of 3-iodo-O-mythyl-L-alpha-methyltyrosine in Tumor Bearing Rats: A Comparison Study with L-3-iodo-alpha-methyltyrosine / 대한핵의학회잡지

PURPOSE: The aim of this sutdy was to evaluate the feasibility of 3-[131I]Iodo-O-methyl-L-a-methyltyrosine ([131I]OMINT) as an agent for tumor image. MATERIALS AND METHODS: After synthesis of 4-O-methyl-L-a-methyltyrosine (OMAMT), OMAMT was labeled with 131I using Iodogen method. In viro cellular uptake study was performed using 9 L gliosarcoma cells at various time points upto 4 hr. The biodistribution (five rats implanted with the 9 L gliosarcoma cells per group) was evaluated at 30 min, 2 hr, 24 hr after iv injection of 3.7 MBq [131I]OMIMT or L-3-[131I]iodo-a-methyltyrosine ([131I]IMT). Gamma camera images were obtained at 30min, 2 hr, and 24 hr. RESULTS: [131I]OMINT uptake was 3.3 times and 2.5 times higher than [131I]IMT uptake at 30 min and 60 min, respectively and same after 2 hr in in vitro sutdy using 9L gliosarcoma cells. Maximum accumulation in tumor occurred at 30 min for both [131IOMINT and [131I]IMT in tumor bearing rats. The tumor uptake of [131I]OMINT was significantly higher than that of [131I]IMT in tumor bearing rats. The tumor uptake of [131I]OMIMT was significantly higher than that of [131I]IMT at early time point studied (3.74 +/- 0.48 vs 0.38 +/- 0.17% ID/g at 30 min and 2.40 +/- 0.17 vs 0.24 +/- 0.03% ID/g at 2 hr, respectively, p<0.01). However, the tumor uptake of both radiolabels were not significantly different at 24 hr (0.04 +/- 0.01 vs 0.05 +/- 0.01% ID/g). Tumor was visualized as early as at 30 min in gamma camera images. CONCLUSION: These data suggested that [131I]OMIMT might be a useful tumor imaging agent and has more advantage for the tumor imaging compared to [131I]IMT.