JP2007217370A - ポジトロン断層撮影法および該方法に用いるポジトロン放出化合物 - Google Patents
ポジトロン断層撮影法および該方法に用いるポジトロン放出化合物 Download PDFInfo
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- XWTAQEXSIBGWRM-UHFFFAOYSA-N phenyl 1,4-diazabicyclo[3.2.2]nonane-4-carboxylate Chemical compound C1CN(CC2)CCC2N1C(=O)OC1=CC=CC=C1 XWTAQEXSIBGWRM-UHFFFAOYSA-N 0.000 description 1
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- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0468—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nuclear Medicine (AREA)
Abstract
【解決手段】本発明方法は、ポジトロン放出源の分布と集積度を測定するポジトロン断層撮影法において、当該ポジトロン放出源として、化合物(I)を用いることを特徴とする。
[式中、Rはポジトロン放出能を有するC1-6アルキル基またはハロゲン原子基を示す。]
【選択図】なし
Description
4−ブロモフェニル 2,5−ジアザビシクロ[3.2.2]ノナン−2−カルボキシレート(1.0g、0.003mol)を乾燥トルエン(30mL)に溶解し、テトラキストリフェニルホスフィンパラジウム(0.18g、0.00015mol)を添加した。次いで、ビストリブチルスズ(4.45g、0.0077mol)を滴下し、加熱還流しつつ16時間攪拌した。反応終了後、反応混合液を濾過し、濾液から溶媒を減圧留去した後に、カラムクロマトグラフィ(NHシリカゲル使用、移動相:n−ヘキサン/酢酸エチル=3/2)で精製することによって、目的化合物を得た(0.7g、収率:43%)。
サイクロトロン(住友重機械工業製、HM−18)を使って18MeVに加速した電子を、純窒素ガスを封入したターゲットへ20μAの電流値で約60分間照射して、14N(p,α)11C核反応により11CO2を得た。この11CO2を、−10℃まで冷却されたLiAlH4の0.1Mテトラヒドロフラン溶液(500μL)へ5分間導入した。次いで、N2ガスによりテトラヒドロフランを留去した後、ヨウ化水素酸(0.5mL)を加えた。生成したCH3Iを蒸留精製した。
トリス(ジベンジリデンアセトン)ジパラジウム(4.5mg)とトリ−O−トリルホスフィン(6.2mg)をジメチルホルムアミド(0.3mL)に溶解し、軽く加熱した。当該溶液へ製造例1−2で得た11CH3Iを加え、放射能が平衡に達した時点で反応器を密閉し、室温で1分間パラジウム錯体と11CH3Iとを反応させた。別途、製造例1−1で得たトリブチルスズ化合物(4mg)と塩化銅(CuCl、1.0mg)、炭酸カリウム(1.4mg)をジメチルホルムアミド(0.3mL)に溶解した。この溶液を11CH3Iの溶液へ加え、70℃で5分間加熱することによりメチル化反応を行なった。得られた反応混合液を下記条件の高速液体クロマトグラフィで精製し、目的化合物(Ia)を得た(7μg、収率:30〜40%)。得られた化合物(Ia)は、生理食塩水(5〜10mL)に溶解し、0.22μmの滅菌フィルターを通して注射剤とした。
高速液体クロマトグラフィの条件
カラム:Megapak SIC C18−10 7.6*250mm(日本分光製)
溶出液:アセトニトリル/30mM酢酸アンモニウム/酢酸=600/400/2
流速:6mL/分
検出波長:220nm
得られた化合物(Ia)の特性は、表1の通りである。
上記製造例1−1で得られた4−トリブチルスズフェニル 1,4−ジアザビシクロ[3.2.2]ノナン−4−カルボキシレート(1mg、1.9μmol)を酢酸の1%エタノール溶液(250μL)に溶解した。別途、市販の[76Br]HBr溶液(住重試験検査社製、15〜20mL)を窒素ガス気流下75℃で約200μLまで濃縮した。この[76Br]HBr溶液(約200μL)へ、製造例1−1の化合物の上記溶液と、クロラミン−Tの200mMエタノール溶液(25μL)を加え、75℃で30分間反応させた。反応終了後、アセトニトリル/(30mM酢酸アンモニウム:1000mL+酢酸:4mL)=1/1の混合溶媒を溶出液とする高速液体クロマトグラフィ(日本分光社製のMegapak SIC C18−10 7.6*250mm、流速:6mL/分、波長:220nm)で精製した。得られた化合物(Ib)の特性は、表2の通りである。
測定実施日前夜から絶食させたアカゲザル(雄、体重5.5kg)をモンキーチェアに座らせ、頭部固定装置により動物用PETカメラ(浜松ホトニクス社製、SHR−7700)のガンドリー内に頭部を固定した。呼吸補正のために、トランスミッション計測を30分間行なった。その後、上記製造例1−3と製造例2で製造した注射剤を、化合物(Ia)で換算して77ng/kg体重、化合物(Ib)で230ng/kg体重の投与量で静脈より投与し、180分間のダイナミック計測を行なった。得られた画像を再構成した後、脳の各部位に関心領域(ROI)を設定し、それぞれの領域における放射能動態を求めた。化合物(Ia)の結果を図2に、化合物(Ib)の結果を図3に示す。
各化合物のα7ニコチン受容体に対する選択性を試験するために、α7ニコチン受容体の選択的アゴニストであるSSR180711A、またはα4β2ニコチン受容体に対する選択性アゴニストであるA85380を事前に投与した上で、化合物(Ia)または(Ib)の取込量を測定した。
Claims (7)
- ポジトロン放出源の分布と集積度を測定するポジトロン断層撮影法において、当該ポジトロン放出源として、化合物(I)を用いることを特徴とするポジトロン断層撮影法。
- 上記ポジトロン放出源として、Rが11CH3である化合物(I)を用いる請求項1に記載のポジトロン断層撮影法。
- 上記ポジトロン放出源として、Rが76Brである化合物(I)を用いる請求項1に記載のポジトロン断層撮影法。
- 上記ポジトロン放出源として、Rの置換位置が4位である化合物(I)を用いる請求項1〜3の何れかに記載のポジトロン断層撮影法。
- ポジトロン放出源である化合物(I)。
- ポジトロン放出源である化合物(Ia)。
- ポジトロン放出源である化合物(Ib)。
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JP2006041545A JP2007217370A (ja) | 2006-02-17 | 2006-02-17 | ポジトロン断層撮影法および該方法に用いるポジトロン放出化合物 |
PCT/JP2007/052852 WO2007094455A1 (ja) | 2006-02-17 | 2007-02-16 | ポジトロン断層撮影法および当該方法に用いるポジトロン放出化合物 |
EP07714382A EP1985313A4 (en) | 2006-02-17 | 2007-02-16 | POSITRON TOMOGRAPHY METHOD AND POSITRON TRANSMITTER COMPOUND FOR USE |
CA002641944A CA2641944A1 (en) | 2006-02-17 | 2007-02-16 | Positron tomography method and positron-emitting compound to be used therein |
US12/223,968 US20090087378A1 (en) | 2006-02-17 | 2007-02-16 | Positron Tomography Method and Positron-Emitting Compound to Be Used Therein |
AU2007215808A AU2007215808B2 (en) | 2006-02-17 | 2007-02-16 | Positron tomography method and positron-emitting compound to be used therein |
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JP2010037232A (ja) * | 2008-08-01 | 2010-02-18 | Chiba Univ | ポジトロン断層撮影法および該方法に用いるポジトロン放出化合物 |
WO2011002096A1 (ja) * | 2009-07-03 | 2011-01-06 | 独立行政法人理化学研究所 | Pet用標識化合物 |
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- 2007-02-16 WO PCT/JP2007/052852 patent/WO2007094455A1/ja active Application Filing
- 2007-02-16 EP EP07714382A patent/EP1985313A4/en not_active Withdrawn
- 2007-02-16 US US12/223,968 patent/US20090087378A1/en not_active Abandoned
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JP5777163B2 (ja) * | 2009-07-03 | 2015-09-09 | 国立研究開発法人理化学研究所 | Pet用標識化合物 |
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US20090087378A1 (en) | 2009-04-02 |
AU2007215808B2 (en) | 2011-08-11 |
WO2007094455A1 (ja) | 2007-08-23 |
CA2641944A1 (en) | 2007-08-23 |
AU2007215808A1 (en) | 2007-08-23 |
EP1985313A4 (en) | 2009-01-21 |
EP1985313A1 (en) | 2008-10-29 |
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