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Moon, Byung Seok,Kil, Hee Seup,Park, Jun Hyung,Kim, Ji Sun,Park, Jimin,Chi, Dae Yoon,Lee, Byung Chul,Kim, Sang Eun Royal Society of Chemistry 2011 Organic & Biomolecular Chemistry Vol.9 No.24
<P>Aromatic radiofluorination of the diaryliodonium tosylate precursor with [<SUP>18</SUP>F]fluoride ions has been applied successfully to access [<SUP>18</SUP>F]flumazenil in high radiochemical yields of 67.2 ± 2.7% (decay corrected). The stability and reactivity of the diaryliodonium tosylate precursor plays a key role in increasing the production of <SUP>18</SUP>F-labelled molecules under the fluorine-18 labelling condition. Various conditions were explored for the preparation of [<SUP>18</SUP>F]flumazenil from different diaryliodonium tosylate precursors. Optimum incorporation of [<SUP>18</SUP>F]fluoride ions in the 4-methylphenyl-mazenil iodonium tosylate precursor (5f) was achieved at 150 °C for 5 min by utilizing 4 mg of the precursor, K<SUB>2.2.2</SUB>/K<SUB>2</SUB>CO<SUB>3</SUB> complex, and the radical scavenger in <I>N</I>,<I>N</I>-dimethylformamide. This approach was extended to a viable method for use in automated synthesis with a radiochemical yield of 63.5 ± 3.2% (decay corrected, <I>n</I> = 26) within 60.0 ± 1.1 min. [<SUP>18</SUP>F]Flumazenil was isolated by preparative HPLC after the reaction was conducted under improved conditions and exhibited sufficient specific activity of 370–450 GBq μmol<SUP>−1</SUP>, with a radiochemical purity of >99%, which will be suitable for human PET studies.</P> <P>Graphic Abstract</P><P>Various conditions were explored using different diaryliodonium tosylate precursors with fluorine-18 for the efficient preparation of [<SUP>18</SUP>F]flumazenil <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c1ob06277h'> </P>
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저혈당성 쇼크로 발현된 덤핑 증후군에서의 Octreotide 치료 효과
홍종민 ( Jong Maen Hong ),최성희 ( Seung Hee Choi ),임홍섭 ( Hong Seup Rim ),차봉수 ( Bong Soo Cha ),임승길 ( Sung Kil Lim ),이현철 ( Hyun Chul Lee ),허갑범 ( Kap Bum Huh ) 대한내과학회 2002 대한내과학회지 Vol.63 No.5
Following gastric surgery, 25~50% of patients experience dumping symptoms. Early dumping usually involves both gastro-intestinal and vasomotor complaints, while late dumping involves mainly the latter. Management is mainly achieved by dietary modification. Drug therapy has been investigated without consistent success. However, the somatostatin analogue octreotide alleviates dumping by slowing gastric emptying, inhibiting insulin release, decreasing enteric peptide secretion and intestinal absorption of water and sodium, slowing monosaccharide absorption, increasing gut transit time and preventing hemodynamic changes. We report a case with the place of octreotide in the medical management of the dumping syndrome. The patient was 71-year-old male who had taken total gastrectomy for gastric cancer in 1987. He had been well except intermittent abdominal pain for 8 years after total gastrectomy. But he had suffered from sudden symptoms such as hypoglycemic shock and fainting, which start 2~3 hours after ingesting of a meal for recent 5 years. Studies for diagnosing insulinoma were all negative. We start diet modification and medication such as acarbose to him with impression of dumping syndrome, but there were no improvement of his symptoms. Then we start octreotide, 50 꺤g, given subcutaneously, three-times per day, 30 min prior to each meal. His symptom was dramatically improved.(Korean J Med 63:567-571, 2002) Key Words : Dumping syndrome, Somatostatin, Octreotide, Hypoglycemia
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김민환,Jung Woon Jung,Jeong Hyeon Jin,Lee Kyongkyu,Kil Hee Seup,Chung Wee Sup,Nam Kyung Rok,Lee Yong Jin,Lee Kyo Chul,Lim Sang Moo,Chi Dae Yoon 대한화학회 2022 Bulletin of the Korean Chemical Society Vol.43 No.6
We investigated the off-target binding of amyloid-beta (Aβ) target [18F] florapronol ([18F]FC119S) using postmortem Alzheimer’s disease (AD) brain tissue, compared with a known Aβ target imaging agent, [125I]TZDM and tau targeting [125I]MK as positive and negative controls, respectively. Off-target binding of monoamine oxidase-A and -B (MAO-A and -B) was screened for FC119S and Pittsburgh compound B (PiB). Autoradiography (ARG) was performed to screen the Aβ-binding potential using human AD postmortem brain tissue sections. Colocalization was quantitatively analyzed by using image analysis software. Pathological analysis was performed for screening of specific binding of amyloid-beta and phospho-tau. Amyloid-beta targeting [18F]FC119S and [125I]TZDM tracers were showed a similar binding pattern in ARG, but [125I] MK was showed a different binding patterns. In the blocking experiment, [18F] FC119S binding was effectively blocked by a cold TZDM compound. FC119S and PiB were not showed specific binding with MAO-A and MAO-B. The autoradiographic binding pattern was positively correlated with the Aβ expression.
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Induced Phenotype Targeted Therapy: Radiation-Induced Apoptosis-Targeted Chemotherapy
Lee, Beom Suk,Cho, Yong Woo,Kim, Gui Chul,Lee, Do Hee,Kim, Chang Jin,Kil, Hee Seup,Chi, Dae Yoon,Byun, Youngro,Yuk, Soon Hong,Kim, Kwangmeyung,Kim, In-San,Kwon, Ick Chan,Kim, Sang Yoon U.S. Dept. of Health, Education, and Welfare, Publ 2015 Journal of the National Cancer Institute Vol.107 No.2
<P><B>Background:</B></P><P>Tumor heterogeneity and evolutionary complexity may underlie treatment failure in spite of the development of many targeted agents. We suggest a novel strategy termed induced phenotype targeted therapy (IPTT) to simplify complicated targets because of tumor heterogeneity and overcome tumor evolutionary complexity.</P><P><B>Methods:</B></P><P>We designed a caspase-3 specific activatable prodrug, DEVD-S-DOX, containing doxorubicin linked to a peptide moiety (DEVD) cleavable by caspase-3 upon apoptosis. To induce apoptosis locally in the tumor, we used a gamma knife, which can irradiate a very small, defined target area. The in vivo antitumor activity of the caspase-3–specific activatable prodrug combined with radiation was investigated in C3H/HeN tumor-bearing mice (n = 5 per group) and analyzed with the Student’s <I>t</I> test or Mann-Whitney U test. All statistical tests were two-sided. We confirmed the basic principle using a caspase-sensitive nanoprobe (Apo-NP).</P><P><B>Results:</B></P><P>A single exposure of radiation was able to induce apoptosis in a small, defined region of the tumor, resulting in expression of caspase-3. Caspase-3 cleaved DEVD and activated the prodrug. The released free DOX further activated DEVD-S-DOX by exerting cytotoxic effects on neighboring tumor or supporting cells, which repetitively induced the expression of caspase-3 and the activation of DEVD-S-DOX. This sequential and repetitive process propagated the induction of apoptosis. This novel therapeutic strategy showed not only high efficacy in inhibiting tumor growth (14-day tumor volume [mm<SUP>3</SUP>] vs radiation alone: 848.21±143.24 vs 2511.50±441.89, <I>P</I> < .01) but also low toxicity to normal cells and tissues.</P><P><B>Conclusion:</B></P><P>Such a phenotype induction strategy represents a conceptually novel approach to overcome tumor heterogeneity and complexity as well as to substantially improve current conventional chemoradiotherapy with fewer sequelae and side effects.</P>
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