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論文 |
論文
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柴, 和弘 ; 森, 厚文 ; 久田, 欣一 ; Shiba, Kazuhiro ; Mori, Hirofumi ; Hisada, Kinichi
概要:
金沢大学疾患モデル総合研究センター<br />We studied the tumor-localizing characteristics of alicyclic alpha-amino acid analogs (a-j) witho
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ut alpha-hydrogen, because of the selective affinity of synthetic nonmetabolizing amino acids such as 1-aminocyclopentanecarboxylic acid (ACPC) and alpha-aminoisobutyric acid alpha-AIB) to tumor tissues. Ten different alicyclic alpha-amino acids (a-j) were labeled with 14C using a modified Bücherer synthesis for amino acids. The tissue distributions and whole-body autoradiographic study of these 14C-labeled alicyclic alpha-amino acid analogs (a-j) were investigated in mice bearing Ehrlich tumor. These results showed that the tumor uptakes and tumor to tissue concentration ratios increased with decreasing ringsize in homologous series (8- through 4-membered ring systems) and alicyclic alpha-amino acid analogs containing 3- or 4-methyl group had the higher tumor to tissue concentration ratios. On the other hand, alicyclic alpha-amino acid analogs containing 2-methyl group and 4-phenyl group showed the lower tumor uptakes and the lower tumor to tissue concentration ratios. These results suggest that the small ringsize alicyclic alpha-amino acid analogs containing 3-methyl group such as 3-methyl-1-aminocyclopentanecarboxylic acid (3-MeACPC) may be effective for the early detection of tumors.<br />腫瘍親和性に優れているa位に水素を有しない脂環式合成アミノ酸である1-aminocyclopentanecarboxylic acid (ACPC) と9種の類似化合物を14Cで標識合成し, これらをニールリッヒ担がんマウスに投与し, 臓器摘出法および全身オートラジオグラフィにて脂環式合成アミノ酸の構造変化 (環の大きさ, 側鎖の種類および位置) による腫瘍親和性の影響についてその相関性を検討した。その結果, 1.amino-3-methylcy clopentanecarboxylic acid (3-MeACPC) のような比較的環の大きさが小さくまたアミノ酸の官能基 (-NH3, -COOH) から離れた位置にメチル基を有する脂環式合成アミノ酸が優れた腫瘍親和性物質としての可能性が示唆された。
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| 2.
論文 |
論文
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森, 厚文 ; 柴, 和弘 ; 辻, 志郎 ; 松田, 博史 ; 久田, 欣一 ; 小島, 一彦 ; Mori, Hirofumi ; Shiba, Kazuhiro ; Tsuji, Shiro ; Matsuda, Hiroshi ; Hisada, Kinichi ; Kojima, Kazuhiko
概要:
金沢大学疾患モデル総合研究センター<br />ラット脳の3H-スピロペリドールによる受容体マクロオートラジオグラフィに関して, 基礎的検討, すなわちインキュベーション時間, 洗浄時間, 飽和実験, 作動薬, 拮抗薬による抑制効果について検
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討するとともに, ビデオカメラとコンピュータを組合せたVideo Digitizer Systemを用いてサブトラクションイメージを作成した。その結果, 本法はドーパミン等の受容体の形態学的分布ならびに動態の解析が可能であり, 神経精神疾患の病態解明ならびに陽電子, あるいは単光子横断断層イメージの解釈に有用と期待された。<br />The kinetic and pharmacological characteristics of 3H-spiroperidol binding sites were studied in slide mounted sections of rat forebrain, and optical binding conditions were defined. Using the receptor macroautoradiographic techniques with tritium-sensitive LKB sheet film, the distribution of dopamine (D2) receptor was determined in slices including striatum of rat brain. The autoradiograms were analyzed using Video Digitizer System combined with video camera and minicomputer, and the subtraction images were obtained.These studies suggest that this quantitative receptor macroautoradiography might be useful in the explanation of etiology in the field of neuro psychiatric diseases and the fundamental studies of positron emission computed tomography, since this method has several advantages over in vivo autoradiography and in vitro receptor assay.
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| 3.
論文 |
論文
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柴, 和弘 ; 森, 厚文 ; 久田, 欣一 ; Shiba, Kazuhiro ; Mori, Hirofumi ; Hisada, Kinichi
概要:
金沢大学疾患モデル総合研究センター<br />14C-標識アミノ酸 (1-aminocyclopentane-1-carboxylic acid, α-amino isobutyric acid, L-leucine, DL-leucine
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) , 糖類似物質 (2-deoxy-2-fluoro-D-glucose) , 核酸前駆物質 (thymidine) をエールリッヒ担がんマウスおよび肝がんAH109A担がんラットに投与し, 臓器摘出法および全身オートラジオグラフィにて腫瘍親和性について比較検討した。その結果, 短半減期ポジトロン核種を用いたポジトロン放射型コンピュータ断層撮影 (ECT) 用には, 胸部領域を除いて糖類似物質, single photon ECT用には, 膵臓, 肝臓を除いて非天然アミノ酸が優れていることが示唆された。<br />As tumor-seeking agents, glucose analogues, natural amino acids, synthetic nonmetabolized amino acids, and precursor of nucleic acids, etc., labeled with positron emitter, such as 11C and 18F have been recently investigated. However, there are very few reports concerning comparative study of tumor uptake and tissue distribution of these agents. This preliminary paper describes comparative distribution and whole-body autoradiography of these agents. 14C labeled deoxy-2-fluoro-D-glucose (FDG), L-, DL-leucine, 1-aminocyclopentane carboxylic acid (ACPC) , α-amino isobutyric acid (α-AIB), and thymidine were intravenously injected through tail vein into separate groups of the experimental animals. As the experimental animals, the mice with Ehrlich tumor and the rats with Hepatoma AH109A were used.Within 30 min after injection, FDG had the highest tumor uptake and tumor to tissue ratios, although FDG was inferior to ACPC and thymidine in related to tumor to heart, lung and brain ratios. However, the time course study indicated that tumor uptake of ACPC, α-AIB and D-leucine increased with time, whereas those of other agents decreased with time or reached a plateau. Thus, at 120 min after injection, ACPC had the highest tumor uptake and tumor to tissue ratios, although ACPC was inferior to FDG in related to tumor to blood, liver and pancreas ratios. Autoradiogram of ACPC showed very clear tumor image as well as that of FDG. The above data suggest that synthetic nonmetabolized amino acids, such as ACPC may be promising as tumor-seeking agents, when used with a single photon emission computed tomography, while glucose analogue such as FDG, are the best tumor-seeking agent, when used with a positron emission computed tomography.
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