JP2008528445A - 放射性標識法 - Google Patents
放射性標識法 Download PDFInfo
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- JP2008528445A JP2008528445A JP2007547612A JP2007547612A JP2008528445A JP 2008528445 A JP2008528445 A JP 2008528445A JP 2007547612 A JP2007547612 A JP 2007547612A JP 2007547612 A JP2007547612 A JP 2007547612A JP 2008528445 A JP2008528445 A JP 2008528445A
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- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000005208 trialkylammonium group Chemical group 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- WHNFPRLDDSXQCL-UAZQEYIDSA-N α-msh Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H](CO)NC(C)=O)C1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UAZQEYIDSA-N 0.000 description 1
Classifications
-
- 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
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
-
- 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
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
-
- 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
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/082—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the peptide being a RGD-containing peptide
-
- 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
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1045—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants
- A61K51/1051—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody against animal or human tumor cells or tumor cell determinants the tumor cell being from breast, e.g. the antibody being herceptin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
Abstract
Description
RA基は各々独立にH又はC1〜10アルキル、C3〜10アルキルアリール、C2〜10アルコキシアルキル、C1〜10ヒドロキシアルキル、C1〜10アルキルアミン、C1〜10フルオロアルキルであるか、或いは2以上のRA基がそれらに結合した原子と共に炭素環、複素環、飽和又は不飽和環を形成するものである。或いは、R*は以下の式(i)、(ii)、(iii)又は(iv)のキレート剤を含むものであってもよい。
DMF:N,N−ジメチルホルムアミド
DMSO:ジメチルスルホキシド
ESI−MS:エレクトロスプレーイオン化質量分析法
rt:室温
TOF−ESI−MS:飛行時間型エレクトロスプレーイオン化質量分析
FT−IR:フーリエ変換赤外
ppm:百万分率
TFA:トリフルオロ酢酸
ACN:アセトニトリル。
化合物(2):1−アジド,2−フルオロエタンの調製
トルエン−4−スルホン酸2−フルオロエチルエステル(化合物(1))はE.U.T. van Velzen他,Synthesis(1995)989−997に記載の通り調製した。化合物(1)(128mg、0.586mmol)及びアジ化ナトリウム(114mg、1.758mmol)を無水DMF(10ml)と混合し、室温で48時間撹拌した。反応混合物を濾過したが、生成物(2)は反応溶液から単離しなかった。
化合物(3):1−(2−フルオロエチル)−4−フェニル−1H−[1,2,3]トリアゾールの調製
DMF(1mL)中のフェニルアセチレン(105μL、0.977mmol)を窒素下で硫酸銅(II)五水和物(12mg、0.0489mmol)とL−アスコルビン酸(16mg、0.0977mmol)の水(0.3mL)中の撹拌溶液に添加した。DMF(5mL)中の化合物(2)(1.172mmol)を添加した後、室温で21時間攪拌を続けた。反応混合物を水(5mL)で希釈し、粗生成物をジクロロメタン(3×5mL)で抽出し、重炭酸ナトリウム溶液(10%、3×10mL)及び塩水(1×5mL)で洗浄した。硫酸ナトリウム上で乾燥した後、溶媒を減圧除去し、粗標品をフラッシュクロマトグラフィー(シリカ、ヘキサン/酢酸エチル)を用いて精製した。
収量:32mg(17%)、白色結晶、m.p.83〜85℃。
1H−NMR(CDCl3):δ=4.70(m,1H,CH2)、4.76(m,1H,CH2)、4.80(m,1H,CH2)、4.89(m,1H,CH2)、7.35(tt,1.0Hz,7.5Hz,1H,HAr)、7.44(m,2H,HAr)、7.84(m,2H,HAr)、7.89(d,1Hz,1H,CH−トリアゾール)ppm。
GC−MS:m/z=191。
TOF−ESI−MS:実測値 m/z=192.0935[MH]+、C10H10N3Fの計算値[MH]+ m/z=192.0932。
化合物(4):4−[1−(2−フルオロエチル)−1H−[1,2,3]トリアゾール−4−イル]−フェニルアミンの調製
DMF(0.7mL)中の4−エチニルアニリン(40mg、0.344mmol)を窒素下で硫酸銅(II)五水和物(129mg、0.516mmol)とL−アスコルビン酸(182mg、1.032mmol)の水(1.2mL)中の撹拌溶液に添加した。DMF(2.45mL)中の化合物(2)(0.287mmol)を添加した後、室温で4時間攪拌を続けた。反応混合物を水酸化ナトリウム溶液(1M、5mL)で奪活した。生成物を酢酸エチル(3×5mL)で抽出し、水(5mL)及び塩水(2mL)で洗浄した。硫酸ナトリウム上で乾燥した後、溶媒を減圧除去し、粗標品をフラッシュクロマトグラフィー(シリカ、ヘキサン/酢酸エチル)を用いて精製した。収量:15mg(25%)、ベージュ結晶、m.p.79〜82℃。
1H−NMR(CDCl3):δ=4.70(m,1H,CH2)、4.72(m,1H,CH2)、4.77(m,1H,CH2)、4.88(m,1H,CH2)、6.74(m,2H,HAr)、7.63(m,2H,HAr)、7.74(d,0.1Hz,1H,CH−トリアゾール)ppm。
TOF−ESI−MS:実測値 m/z=207.1030[MH]+、C10H11N4Fの計算値[MH]+ m/z=207.1040。
化合物(5):1−(2−フルオロエチル)−1H−[1,2,3]トリアゾール−4−カルボン酸ベンジルアミドの調製
G.M.Coppola & R.E.Damon, Synthetic Communications 23(1993)2003−2010に記載の方法で調製したプロピン酸ベンジルアミド(50mg、0.314mmol)をDMF(1mL)中に溶解し、窒素下で硫酸銅(II)五水和物(3.9mg、0.0157mmol)とL−アスコルビン酸(11mg、0.0628mmol)の水(0.4mL)中の撹拌溶液に添加した。DMF(3.2mL)中の化合物(2)(0.377mmol)を添加した後、室温で48時間攪拌を続けた。反応混合物を重炭酸ナトリウム(10%、5mL)で希釈し、粗生成物をジクロロメタン(3×5mL)で抽出し、塩水(5mL)で洗浄した。硫酸ナトリウム上で乾燥した後、溶媒を減圧除去し、粗標品を酢酸エチル/ジエチルエーテルからの再結晶によって精製した。
収量:8mg(10%)、白色結晶、m.p.165〜167℃。
1H−NMR(CDCl3):δ=4.70(m,6H,CH2)、7.34(m,5H,HAr)、7.46(m,1H,NH)、8.20(s,1H,CH−トリアゾール)ppm。
TOF−ESI−MS:実測値 m/z=249.1143[MH]+、C12H13N4OFの計算値[MH]+ m/z=249.1146。
化合物(6):N−ベンジル−3−[1−(2−フルオロエチル)−1H−[1,2,3]トリアゾール−4−イル]プロピオンアミドの調製
ペント−4−イン酸ベンジルアミド:この化合物は、N−スクシニミジル中間体の単離以外は、G.M.Coppola及びR.E.Damonに記載の方法(実施例4参照)と同様の方法を用いて合成した。
収量:100mg(53%)、白色針状晶、m.p.50〜55℃。
1H−NMR(CDCl3):δ=1.98(m,1H,アルキン−CH)、2.44(m,2H,CH2)、2.56(m,2H,CH2)、4.46(d,2H,CH2N)、7.29〜7.25(m,5H,HAr)ppm。
FT−IR(フィルム):1651、1629cm−1。
TOF−ESI−MS:実測値 m/z=188.1073[MH]+、C12H13NOの計算値[MH]+ m/z=188.1070。
収量:19mg(26%)、白色結晶、m.p.127〜133℃。
1H−NMR(CDCl3):δ=2.66(t,7.0Hz,2H,CH2)、3.09(t,7.0Hz,2H,CH2)、4.40(d,5.7Hz,2H,ベンジル−CH2)、4.56(m,2H,CH2)、4.61(m,2H,CH2)、4.70(m,2H,CH2)、4.80(m,2H,CH2)、6.0(s,1H,NH)、7.0〜7.3(m,5H,HAr)、7.44(s,1H,CH−トリアゾール)ppm。
TOF−ESI−MS:実測値 m/z=277.1474[MH]+、C12H13N4OFの計算値[MH]+ m/z=277.1459。
化合物(7):4−[1−(2−フルオロエチル)−1H−[1,2,3]トリアゾール−4−イル]安息香酸の調製
DMF(1.5mL)中の4−エチニル安息香酸ナトリウム(50mg、0.297mmol)を窒素下で硫酸銅(II)五水和物(3.7mg、0.0149mmol)とL−アスコルビン酸(10.5mg、0.0595mmol)の水(0.2mL)中の撹拌溶液に添加した。DMF(0.76mL)中の化合物(2)(0.356mmol)を添加した後、室温で12時間攪拌を続けた。反応混合物をHCl(20mL、1M)で希釈した。粗生成物を酢酸エチル(3×10mL)で抽出し、塩水(10mL)で洗浄した。硫酸ナトリウム上で乾燥した後、溶媒を減圧除去し、粗標品を酢酸エチル/ヘキサンから再結晶した。
収量:37mg(52%)、白色結晶、m.p.236〜240℃。
1H−NMR(DMSO−d6):δ=4.74(m,1H,CH2)、4.80(m,2H,CH2)、4.90(m,1H,CH2)、8.70(s,1Hz,1H,CH−トリアゾール)ppm。
TOF−ESI−MS:実測値 m/z=236.0838[MH]+、C11H10N3O2Fの計算値[MH]+ m/z=236.0830。
化合物(8):1−(2−フルオロエチル)−1H−[1,2,3]トリアゾール−4−カルボン酸の調製
DMF(0.5mL)中のプロピオル酸(60μL、0.977mmol)を窒素下で硫酸銅(II)五水和物(12mg、0.0489mmol)とL−アスコルビン酸(34mg、0.135mmol)の水(0.4mL)中の撹拌溶液に添加した。DMF(2.5mL)中の化合物(2)(1.172mmol)を添加した後、室温で4時間攪拌を続けた。反応混合物をHCl(20mL、1M)で奪活し、粗生成物を酢酸エチル(3×20mL)で抽出した。塩水(5mL)で洗浄し、硫酸ナトリウム上で乾燥した後、溶媒を減圧除去し、生成物を酢酸エチル/ヘキサンからの再結晶によって精製した。
収量:16mg(10%)、白色結晶、m.p.160〜165℃。
1H−NMR(DMSO−d6):δ=4.74(m,1H,CH2)、4.80(m,2H,CH2)、4.90(m,1H,CH2)、8.71(s,1H,CH−トリアゾール)ppm。
TOF−ESI−MS:実測値 m/z=160.0518[MH]+、C5H6N3O2Fの計算値[MH]+ m/z=160.0517。
化合物(9):2−アセチルアミノ−3−[1−(2−フルオロエチル)−1H−[1,2,3]トリアゾール−4−イル]プロピオン酸エチルエステルの調製
メタノール(1mL)中の2−アセチルアミノペント−4−イン酸エチルエステル(200mg、1.09mmol)を窒素下で銅粉(200mg、40メッシュ)に添加した後、化合物(2)(1.09mmol)のDMF(3mL)溶液を添加した。混合物を90分間撹拌した後、80℃で3時間加熱した。化合物(9)を逆相フラッシュクロマトグラフィー(アセトニトリル/水)で単離した。
収量:145mg(49%)、油、4℃の保存で結晶、m.p.55〜60℃。
1H−NMR(CDCl3):δ=1.13(t,3H,CH2CH3)、1.82(s,3H,CH3)、2.97(dd,2J=14.9Hz,3J=8.5Hz,1H,プロピオン酸−CH2)、3.07(dd,2J=14.9Hz,3J=6.0Hz,1H,プロピオン酸−CH2)、4.05(m,2H,OCH2CH3)、4.47(m,1H,CH)、4.46(m,1H,CH2)、4.64(m,1H,CH2)、4.70(m,1H,CH2)、4.81(m,1H,CH2)、7.89(s,1H,トリアゾール−CH)、8.31(d,1H,NH)ppm。
TOF−ESI−MS:実測値 m/z=273.1372[MH]+、C11H17N4O3Fの計算値[MH]+ m/z=273.1357。
化合物(11):[ 18 F]1−アジド−2−フルオロエタンの調製
18Fフッ化物は、濃縮[18O]H2Oターゲットの19MeVプロトン照射による18O(p,n)18F核反応を用いたサイクロトロンで生成した。照射後、Kryptofix(登録商標)(5mg)、炭酸カリウム(1mg)及びアセトニトリル(1mL)の混合物を18F水(1mL)に添加した。窒素気流下(100mL/分)で80℃に加熱して、溶媒を除去した。しかる後、アセトニトリル(0.5mL)を添加し、加熱・窒素気流下で蒸発させた。この操作を2回繰り返した。室温に冷却後、化合物(10)(1.5μl:Z.P.Demko and K.B.Sharpless,Org.Lett.3(2001)4091に記載の方法で調製)の無水アセトニトリル(0.2mL)溶液を添加した。反応混合物を80℃で30分間撹拌した。化合物(11)を、40±14%(n=7)の崩壊補正放射化学収率で蒸留(効率76±8%(n=7))によって単離した。
化合物(12)〜(16):[ 18 F]1−(2−フルオロエチル)−1H−[1,2,3]トリアゾール類の調製
化合物(18):[ 18 F](S)−6−アミノ−2−(2−{(S)−2−[2−((S)−6−アミノ−2−{[4−(2−フルオロエチル)−[1,2,3]トリアゾール−1−カルボニル]アミノ}ヘキサノイルアミノ)アセチルアミノ]−3−フェニルプロピオニルアミノ}アセチルアミノ)ヘキサン酸の調製
化合物(20)の調製
Ac−DL−Pra−OH(31mg)、(7−アザベンゾトリアゾール−1−イロキシ)トリピロリジノホスホニウムヘキサフルオロホスフェート(PyAOP)(104mg)及びN−メチルモルホリン(NMM)(88μL)をジメチルホルムアミド(DMF)中に溶解し、混合物を5分撹拌した後、国際公開第2005/003166号に記載の通り調製してDMF(4mL)に溶解したClCH2CO−Lys−Cys(tBu)−Arg−Gly−Asp−Cys(tBu)−Phe−Cys−PEG−NH2(126mg)を添加した。反応混合物を45分間撹拌した。追加のClCH2CO−Lys−Cys(tBu)−Arg−Gly−Asp−Cys(tBu)−Phe−Cys−PEG−NH2(132mg)及びNMM(44μL)を添加し、45分間攪拌を続けた。次いでDMFを真空下で蒸発させ、残渣(5mL)を10%アセトニトリル(ACN)/水(100mL)で希釈し、分取HPLCで生成物を精製した。
分取HPLC(勾配:A=H2O/0.1%TFA及びB=ACN/0.1%TFAの場合に10〜40%Bを60分、流速:50mL/分、カラム:Phenomenex Luna 5μ C18(2)250×50mm、検出:UV 214nm、生成物保持時間:31.3分)による希釈残渣の精製で、純粋AH−112145を170mg得た。
化合物(19)(0.5mg、0.35μmol)をリン酸ナトリウム緩衝液(pH6.0、50mM)中に溶解し、化合物(11)(25μl、728μCi/25MBq)の溶液及び銅粉(200mg、40メッシュ)と混合した。70℃、15分間加熱後、混合物を放射性HPLCで分析する。
化合物(20)を調製するための反応パラメーターの最適化
一般的手順:緩衝液(50μl、緩衝液A:リン酸ナトリウム、pH6.0、50mM;緩衝液B:炭酸ナトリウム、pH9.3、50mM)中の化合物(19)(0.5mg、0.35μmol)の溶液に、アセトニトリル(100μl)中の化合物(11)(0.1mCi、3.7MBq)を添加した後、銅触媒(触媒1:銅顆粒10〜40メッシュ、触媒2:銅粉約40メッシュ、触媒3:銅粉、樹枝状、3μm)を添加する。混合物を80℃、15分間インキュベートした後、HPLCで分析した。
Claims (18)
- R*が陽電子放出核種、好ましくは11C又は18Fを含む、請求項1記載の方法。
- 前記ベクターが、ペプチド、タンパク質、ホルモン、細胞、細菌、ウィルス又は薬物様低分子、最も好適にはペプチドである、請求項1又は請求項2記載の方法。
- 前記ベクターが、Arg−Gly−Aspペプチド又はその類似体である、請求項1乃至請求項3のいずれか1項記載の方法。
- 元素態銅をCu(I)触媒の供給源として用いる、請求項1乃至請求項6のいずれか1項記載の方法。
- 前記元素態銅が0.001〜1mm、好ましくは0.1mm〜0.7mmの範囲、さらに好ましくは約0.4mmの粒径を有する、請求項7記載の方法。
- 前記ベクターがArg−Gly−Aspペプチド又はその類似体である、請求項10記載の式(V)又は(VI)の化合物。
- 請求項10乃至請求項12のいずれか1項記載の化合物の有効量を、1種以上の薬学的に許容される補助剤、賦形剤又は希釈剤と共に含んでなる放射性医薬組成物。
- 医療用の、請求項10乃至請求項12のいずれか1項記載の化合物。
- インビボイメージング法に用いられる放射性医薬品の製造における、請求項10乃至請求項12のいずれか1項記載の化合物の使用。
- 請求項10乃至請求項12のいずれか1項記載の化合物をヒト又は動物の身体に投与して化合物が分配された身体の少なくとも一部分の画像をPETを用いて生成することを含んでなる、ヒト又は動物の身体の画像生成方法。
- 癌(好ましくは血管新生)に関連した病態に対処するための薬剤によるヒト又は動物の身体の治療効果をモニターする方法であって、請求項10乃至請求項12のいずれか1項記載の化合物を身体に投与し、細胞受容体による上記化合物の取り込みを検出し、任意ではあるが好ましくは、上記投与と検出を、上記薬剤による治療の前後途中に繰り返すことを含んでなる方法。
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PCT/GB2005/004729 WO2006067376A2 (en) | 2004-12-22 | 2005-12-09 | Radiolabelled conjugates of rgd-containing peptides and methods for their preparation via click-chemistry |
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JP2012519176A (ja) * | 2009-02-27 | 2012-08-23 | ジェネンテック, インコーポレイテッド | タンパク質標識方法及び組成物 |
JP2013502400A (ja) * | 2009-08-20 | 2013-01-24 | ジーイー・ヘルスケア・リミテッド | 放射性ヨウ素化方法 |
JP2016047824A (ja) * | 2009-08-20 | 2016-04-07 | ジーイー・ヘルスケア・リミテッド | 放射性ヨウ素化方法 |
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JP2016028096A (ja) * | 2009-12-10 | 2016-02-25 | ジーイー・ヘルスケア・リミテッド | ヨウ素放射性標識法 |
WO2014065413A1 (ja) * | 2012-10-26 | 2014-05-01 | 日本たばこ産業株式会社 | トリアゾール・イソオキサゾール化合物およびその医薬用途 |
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RU2007122804A (ru) | 2009-01-27 |
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US20110236311A1 (en) | 2011-09-29 |
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WO2006067376A2 (en) | 2006-06-29 |
WO2006067376A3 (en) | 2007-07-26 |
CA2589136A1 (en) | 2006-06-29 |
CN105012972A (zh) | 2015-11-04 |
EP2266629B1 (en) | 2015-12-09 |
US7972588B2 (en) | 2011-07-05 |
CA2817636A1 (en) | 2006-06-29 |
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JP5743372B2 (ja) | 2015-07-01 |
AU2005317903B8 (en) | 2012-01-19 |
CA2589136C (en) | 2015-10-06 |
KR20070091626A (ko) | 2007-09-11 |
EP2258403A1 (en) | 2010-12-08 |
AU2005317903C1 (en) | 2012-05-10 |
EP2266629A1 (en) | 2010-12-29 |
BRPI0519317A2 (pt) | 2009-01-13 |
JP2012254998A (ja) | 2012-12-27 |
CN101084020A (zh) | 2007-12-05 |
US8679455B2 (en) | 2014-03-25 |
RU2419627C2 (ru) | 2011-05-27 |
KR101314460B1 (ko) | 2013-10-10 |
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