JP2020125343A - フタロシアニンプローブ及びその使用 - Google Patents
フタロシアニンプローブ及びその使用 Download PDFInfo
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- JP2020125343A JP2020125343A JP2020079840A JP2020079840A JP2020125343A JP 2020125343 A JP2020125343 A JP 2020125343A JP 2020079840 A JP2020079840 A JP 2020079840A JP 2020079840 A JP2020079840 A JP 2020079840A JP 2020125343 A JP2020125343 A JP 2020125343A
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- 239000000523 sample Substances 0.000 title claims abstract description 209
- IEQIEDJGQAUEQZ-UHFFFAOYSA-N phthalocyanine Chemical compound N1C(N=C2C3=CC=CC=C3C(N=C3C4=CC=CC=C4C(=N4)N3)=N2)=C(C=CC=C2)C2=C1N=C1C2=CC=CC=C2C4=N1 IEQIEDJGQAUEQZ-UHFFFAOYSA-N 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 64
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 56
- 150000003384 small molecules Chemical class 0.000 claims abstract description 52
- 239000000203 mixture Substances 0.000 claims abstract description 21
- 239000001007 phthalocyanine dye Substances 0.000 claims abstract description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 50
- -1 FPPRGD2 Chemical compound 0.000 claims description 37
- 239000003112 inhibitor Substances 0.000 claims description 29
- 239000003446 ligand Substances 0.000 claims description 27
- 108010011459 Exenatide Proteins 0.000 claims description 20
- 229960001519 exenatide Drugs 0.000 claims description 20
- 229960005534 chlorotoxin Drugs 0.000 claims description 19
- 101710164760 Chlorotoxin Proteins 0.000 claims description 18
- 102100036519 Gastrin-releasing peptide Human genes 0.000 claims description 18
- 201000011510 cancer Diseases 0.000 claims description 18
- QPAKKWCQMHUHNI-GQIQPHNSSA-N chlorotoxin Chemical group C([C@H]1C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H]4CSSC[C@@H](C(N[C@@H](CCSC)C(=O)N5CCC[C@H]5C(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)CNC(=O)[C@H](CSSC[C@H](NC(=O)[C@H](CC(C)C)NC2=O)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC4=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N3)=O)NC(=O)[C@@H](N)CCSC)C1=CC=C(O)C=C1 QPAKKWCQMHUHNI-GQIQPHNSSA-N 0.000 claims description 18
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 18
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 claims description 16
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- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 claims description 15
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- VBUWHHLIZKOSMS-RIWXPGAOSA-N invicorp Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 VBUWHHLIZKOSMS-RIWXPGAOSA-N 0.000 claims description 14
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- 239000003795 chemical substances by application Substances 0.000 claims description 13
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- 102400000322 Glucagon-like peptide 1 Human genes 0.000 claims description 12
- 102000005157 Somatostatin Human genes 0.000 claims description 12
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 claims description 12
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- 102100025841 Cholecystokinin Human genes 0.000 claims description 11
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 claims description 11
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- QVFLVLMYXXNJDT-CSBVGUNJSA-N (2s,3r)-2-[[(4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-7-[(1r)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-19-[[(2r)-3-phenyl-2-[[2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]pro Chemical compound C([C@H](C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC1=O)C(=O)N[C@@H]([C@H](O)C)C(O)=O)NC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1)C1=CC=CC=C1 QVFLVLMYXXNJDT-CSBVGUNJSA-N 0.000 claims description 10
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- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical group C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 9
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- WCWUXEGQKLTGDX-LLVKDONJSA-N (2R)-1-[[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methyl-6-pyrrolo[2,1-f][1,2,4]triazinyl]oxy]-2-propanol Chemical compound C1=C2NC(C)=CC2=C(F)C(OC2=NC=NN3C=C(C(=C32)C)OC[C@H](O)C)=C1 WCWUXEGQKLTGDX-LLVKDONJSA-N 0.000 claims description 8
- RZHKDBRREKOZEW-AAXZNHDCSA-N 2-[4-[2-[[(2r)-1-[[(4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-4-[[(2r,3r)-1,3-dihydroxybutan-2-yl]carbamoyl]-7-[(1r)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicos-19-yl] Chemical compound C([C@H](C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)NC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1)C1=CC=CC=C1 RZHKDBRREKOZEW-AAXZNHDCSA-N 0.000 claims description 8
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Abstract
Description
本願は、2014年6月2日出願の米国仮特許出願第62/006,790号;;2014年6月25日出願の米国仮特許出願第62/017,165号;2014年10月21日出願の米国仮特許出願第62/066,807号及び2014年11月19日出願の米国仮特許出願第62/082,052号の優先権を主張するものであり、そのすべての教示の全体を、あらゆる目的のために参照によって本明細書中に援用する。
I.序論
II.定義
III.実施形態の詳細な説明
A.プローブにコンジュゲートしたフタロシアニン染料
B.プローブ
1.リガンド
2.ペプチド
3.小分子
C.生体分子プローブへのIRDye(登録商標)700DXのコンジュゲート
−X1−Y1−X2−
式中、X1は、二価のラジカル、直接的な連結、酸素、適宜置換された窒素、及び硫黄から成る群から選択されるメンバーであり;Y1は、直接的な連結及びヘテロ原子が適宜差し込まれたC1−C10アルキレンから成る群から選択されるメンバーであり;及びX2は、二価のラジカル、直接的な連結、酸素、適宜置換された窒素、及び硫黄から成る群から選択されるメンバーである。
IRDye(登録商標)700DX−O−(CH2)3−OC(O)−NH−(CH2)5−C(O)NH−プローブ
D.IRDye(登録商標)700DX標識生体分子プローブの治療的使用
以下の実施例は例証のために提供するものであり、本発明の請求の範囲を限定するために提供するものではない。
実施例1.pH2.1〜8.2及び様々な温度におけるIRDye(登録商標)700DXカルボキシレートの安定性
実施例2.タンパク質へのIRDye(登録商標)700DXカルボキシレートの結合
実施例3.細胞毒性を誘発するための、プローブをコンジュゲートしたIRDye(登録商標)700DXの使用
NIを伴ったIRDye(登録商標)700DX−EGFとのインキュベーションを含む追加対照もまた、細胞形態に有害な影響がないことを示し、PDTにおける照射の必要性を実証した(図6C)。最後に、細胞がIRDye(登録商標)700DX−EGFで処置され、照射を受けたとき、それらの形態は核の縮合及び細胞脱水状態を伴って劇的に変化した(図6D)。これらはアポトーシス及び/又はネクローシスを受けている細胞の重要な特色である。細胞生存率を照射後24時間に評価したとき、結果では、照射で処置したプローブだけが細胞毒性を誘発したことを確認した(図6A〜6D)。
実施例4.動物モデルにおけるIRDye(登録商標)700DXカルボキシレートのクリアランス評価
腎臓(4nmole用量)の隅から隅までの長軸方向の切片は、染料の主要な位置が腎皮質の近位尿細管内であったことを示した。これは染料の濃度にかかわらず、すべての動物に見られた。画像化したすべての臓器(筋肉、心臓、肺、肝臓、脳、脾臓、腸、及び腎臓)を、面積に関して補正したシグナルについて分析した。グラフ表示は図10Cに示す。興味深いことに、用量は腎臓内に滞留した染料の量に劇的なくらい影響しなかった。これは、染料が身体によって絶えず、非常に素早くクリアランスされることを示唆し得る。
実施例5.IRDye(登録商標)700DX−標識抗体、パニツムマブの治療効果の評価
実施例8.クロロトキシンをコンジュゲートしたIRDye(登録商標)700DX(CLTX−700DX)の作製
実施例9.IRDye(登録商標)700Dx小分子コンジュゲート−IRDye(登録商標)700DX標識CLTX(クロロトキシン)及びIRDye(登録商標)700DX標識抗EGFR Affibody(登録商標)の特徴づけ
A.IRDye(登録商標)700DX標識CLTX
B.IRDye(登録商標)700DX標識抗EGFR Affibody(登録商標)
IRDye(登録商標)700DX標識抗体で処置した細胞で見られたものと同様に見える劇的な形態変化を呈した。健常でない細胞はこれらの処置と共に観察された。IRDye(登録商標)700DX標識小分子プローブは、IRDye(登録商標)700DX標識抗体よりも細胞を殺滅するのにより長く(より多くの時間)かかることに注意しなければならない。アポトーシスはより長期間にわたって起こるので、IRDye(登録商標)700DX標識小分子プローブがアポトーシスを誘発し、IRDye(登録商標)700DX標識抗体がネクローシスを誘発するのは明らかである。
実施例10.IRDye(登録商標)700Dx小分子コンジュゲートプローブによるアポトーシス誘発
実施例11.一重項酸素の産生
略式の配列表
配列番号1
EGF
NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR
配列番号2
TNFR1インヒビターペプチド
YCWSQYLCY
配列番号3
血管作動性小腸ペプチド
HSDAVFTDNYTRLRKQMAVK YLNSILN
配列番号4
ボンベシン
Pyr-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met
配列番号5
サブスタンスP
RPKPQQFFGLM
配列番号6
SPARCペプチド
CFGIKQKDIDKDLVI
配列番号7
オクトレオチド
H-D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr(ol)
配列番号8
エキセンジン−4
HGEGTFTSDLSKQMEEEAVRLFIEWLKNGGPSSGAPPPS-NH2
配列番号9
SOR−C13
KEFLHPSKVDLPR
配列番号10
SOR−C27
EGKLSSNDTEGGLCKEFLHPSKVDLPR
配列番号11
ソリシジン
DCSQDCAACSILARPAELNTETCILECEGKLSSNDTEGGLCKEFLHPSKVDLPR
配列番号12
クロロトキシン(CLTX)
MCMPCFTTDHQMARKCDDCCGGKGRGKCYGPQCLCR-NH2
配列番号13
Claims (49)
- 疾患又は病態を患っている対象において細胞毒性を誘発する方法であって:
(a)対象の細胞に特異的に結合するプローブにコンジュゲートしたIRDye(登録商標)700DXなどのフタロシアニン染料を包含する治療的に有効な薬剤を該対象に投与し;そして、
(b)細胞死を誘発するのに有効な量で適切な励起光を前記細胞に照射すること、
を含む、方法。 - 前記疾患又は病態が、血管疾患、癌、細菌性バイオフィルムに起因する感染、抗生物質抵抗性創傷感染、光線性角化症、酒さ、にきび、乾癬から成る群から選択される、請求項1に記載の方法。
- 前記血管疾患が滲出型加齢性黄斑変性症である、請求項2に記載の方法。
- 前記癌が、乳癌、結腸直腸癌、食道癌、肺癌、前立腺癌、子宮頚癌、卵巣癌、胃癌、膵臓癌、肝臓癌、膀胱癌、脳腫瘍、頭頚部癌、神経内分泌系の癌、皮膚癌、及びその組み合わせから成る群から選択される、請求項1に記載の方法。
- 前記対象が、固形腫瘍を患っているか又は固形腫瘍を患っていた、請求項1に記載の方法。
- 前記細胞が固形腫瘍内又は対象の血中に存在している、請求項5に記載の方法。
- 前記励起光が660〜740nmの波長を有する、請求項1に記載の方法。
- 前記プローブが、リガンド、ペプチド、小分子、及びその組み合わせから成る群から選択される、請求項1に記載の方法。
- 前記プローブが約50kDa未満の分子量を有する、請求項8に記載の方法。
- 前記プローブが約10kDa未満の分子量を有する、請求項8に記載の方法。
- 前記リガンドがEGFである、請求項8に記載の方法。
- 前記ペプチドが、YC−27、cRGDfK、血管作動性小腸ペプチド、ガストリン放出ペプチド、ニューロテンシン、AH111585、FPPRGD2、PK11195、SPARC、ボンベシン、ニューロテンシン、サブスタンスP、ソマトスタチン、コレシストキニン、グルカゴン様ペプチド−1、ニューロペプチドY、オクトレオチド、DOTA−TOC、DOTA−TATE、エキセンジン−4、その類似体、その誘導体、及びその組み合わせから成る群から選択される、請求項8に記載の方法。
- 前記ペプチドが、ソリシジン、SOR−13、及びSOR−C27から成る群から選択される、請求項8に記載の方法。
- 前記小分子が、VEGFR阻害剤、TNFR1阻害剤、成長因子受容体阻害剤、及びその組み合わせから成る群から選択される、請求項8に記載の方法。
- 前記小分子VEGFR阻害剤が、パゾパニブ、セマキシニブ、アキシチニブ、カボザンチニブ、アフリベルセプト、ブリバニブ、チボザニブ、ラムシルマブ、モテサニブ、バタラニブ、セジラニブ、及びその組み合わせから成る群から選択される、請求項14に記載の方法。
- 前記プローブが放射性核種にコンジュゲートされる、請求項1に記載の方法。
- 前記プローブが、DTPA−オクトレオチド、[Gluc−Lys]−TOCA、ガラクト−RGD、AH111585、RGD−K5、FPPRGD2、RP−527、BZH3、[DTPA−Lys40]−エキセンジン−4、及びTc−NT−X1から成る群から選択されるメンバーである、請求項16に記載の方法。
- 前記プローブがフルオロフォアにコンジュゲートされる、請求項1に記載の方法。
- 前記ステップ(a)の投与が、治療的に有効な薬剤を対象の血中に注射することを含む、請求項1に記載の方法。
- 前記ステップ(b)の照射が、近赤外(NIR)発光ダイオードを備えたデバイスを使用することを含む、請求項1に記載の方法。
- 抗癌剤を対象に投与することを更に含む、請求項1に記載の方法。
- 癌を患っている対象の固形腫瘍を処置する方法であって:
(a)固形腫瘍の細胞に特異的に結合するプローブにコンジュゲートしたフタロシアニン染料IRDye(登録商標)700DXを包含する治療的に有効な薬剤を対象に投与し、そして、
(b)固形腫瘍のサイズを低減するのに有効な量で適切な励起光を固形腫瘍に照射すること、
を含む、方法。 - 前記固形腫瘍が、乳房の腫瘍、結腸直腸の腫瘍、肺の腫瘍、前立腺の腫瘍、卵巣の腫瘍、胃の腫瘍、膵臓の腫瘍、肝臓の腫瘍、膀胱の腫瘍、脳腫瘍、神経内分泌系の腫瘍、及びその組み合わせから成る群から選択される、請求項22に記載の方法。
- 前記励起光が660〜740nmの波長を有する、請求項22に記載の方法。
- 前記プローブが、リガンド、ペプチド、小分子、及びその組み合わせから成る群から選択される、請求項22に記載の方法。
- 前記プローブが約50kDa未満の分子量を有する、請求項25に記載の方法。
- 前記プローブが約10kDa未満の分子量を有する、請求項25に記載の方法。
- 前記リガンドがEGFである、請求項25に記載の方法。
- 前記ペプチドが、YC−27、cRGDfK、血管作動性小腸ペプチド、ガストリン放出ペプチド、ニューロテンシン、AH111585、FPPRGD2、PK11195、SPARC、ボンベシン、ニューロテンシン、サブスタンスP、ソマトスタチン、コレシストキニン、グルカゴン様ペプチド−1、ニューロペプチドY、オクトレオチド、DOTA−TOC、DOTA−TATE、エキセンジン−4、その類似体、その誘導体、及びその組み合わせから成る群から選択される、請求項25に記載の方法。
- 前記ペプチドが、ソリシジン、SOR−13、及びSOR−C27から成る群から選択される、請求項25に記載の方法。
- 前記小分子が、VEGFR阻害剤、TNFR1阻害剤、成長因子受容体阻害剤、及びその組み合わせから成る群から選択される、請求項25に記載の方法。
- 前記小分子VEGFR阻害剤が、パゾパニブ、セマキシニブ、アキシチニブ、カボザンチニブ、アフリベルセプト、ブリバニブ、チボザニブ、ラムシルマブ、モテサニブ、バタラニブ、セジラニブ、及びその組み合わせから成る群から選択される、請求項31に記載の方法。
- 前記プローブが放射性核種にコンジュゲートされる、請求項22に記載の方法。
- 前記プローブが、DTPA−オクトレオチド、[Gluc−Lys]−TOCA、ガラクト−RGD、AH111585、RGD−K5、FPPRGD2、RP−527、BZH3、[DTPA−Lys40]−エキセンジン−4、及びTc−NT−X1から成る群から選択されるメンバーである、請求項33に記載の方法。
- 前記プローブがフルオロフォアにコンジュゲートされる、請求項22に記載の方法。
- 前記照射が、近赤外(NIR)発光ダイオードを備えたデバイスを使用することを含む、請求項22に記載の方法。
- 抗癌剤を対象に投与することを更に含む、請求項22に記載の方法。
- 対象の癌細胞に特異的に結合するプローブにコンジュゲートしたフタロシアニン染料を包含する治療的に有効な組成物であって、ここで、該プローブが約50kDa未満の分子量を有する組成物。
- 前記プローブが約10kDa未満の分子量を有する、請求項38に記載の組成物。
- 前記プローブが、リガンド、ペプチド、小分子、及びその組み合わせから成る群から選択される、請求項38に記載の組成物。
- 前記リガンドがEGFである、請求項40に記載の組成物。
- 前記ペプチドが、YC−27、cRGDfK、血管作動性小腸ペプチド、ガストリン放出ペプチド、ニューロテンシン、AH111585、FPPRGD2、PK11195、SPARC、ボンベシン、ニューロテンシン、サブスタンスP、ソマトスタチン、コレシストキニン、グルカゴン様ペプチド−1、ニューロペプチドY、オクトレオチド、DOTA−TOC、DOTA−TATE、エキセンジン−4、その類似体、その誘導体、及びその組み合わせから成る群から選択される、請求項40に記載の組成物。
- 前記ペプチドが、ソリシジン、SOR−13、及びSOR−C27から成る群から選択される、請求項40に記載の組成物。
- 前記小分子が、VEGFR阻害剤、TNFR1阻害剤、成長因子受容体阻害剤、及びその組み合わせから成る群から選択される、請求項40に記載の組成物。
- 前記小分子VEGFR阻害剤が、パゾパニブ、セマキシニブ、アキシチニブ、カボザンチニブ、アフリベルセプト、ブリバニブ、チボザニブ、ラムシルマブ、モテサニブ、バタラニブ、セジラニブ、及びその組み合わせから成る群から選択される、請求項44に記載の組成物。
- 前記プローブが放射性核種にコンジュゲートされる、請求項38に記載の組成物。
- 前記プローブが、DTPA−オクトレオチド、[Gluc−Lys]−TOCA、ガラクト−RGD、AH111585、RGD−K5、FPPRGD2、RP−527、BZH3、[DTPA−Lys40]−エキセンジン−4、及びTc−NT−X1から成る群から選択されるメンバーである、請求項46に記載の組成物。
- 前記プローブがフルオロフォアにコンジュゲートされる、請求項38に記載の組成物。
- 前記ペプチドはクロロトキシンである、請求項40に記載の組成物。
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CA2950299A1 (en) | 2015-12-10 |
WO2015187651A1 (en) | 2015-12-10 |
US20200179514A1 (en) | 2020-06-11 |
US20150343060A1 (en) | 2015-12-03 |
US10064943B2 (en) | 2018-09-04 |
EP3148583B1 (en) | 2020-04-29 |
JP2017524659A (ja) | 2017-08-31 |
CN112999347A (zh) | 2021-06-22 |
EP3718570A1 (en) | 2020-10-07 |
US20150374819A1 (en) | 2015-12-31 |
JP6741599B2 (ja) | 2020-08-19 |
CN106573054A (zh) | 2017-04-19 |
JP2022023175A (ja) | 2022-02-07 |
WO2015187677A1 (en) | 2015-12-10 |
EP3148583A4 (en) | 2018-01-17 |
CN106573054B (zh) | 2021-04-13 |
AU2015271830B2 (en) | 2020-03-05 |
US10588972B2 (en) | 2020-03-17 |
US20150343084A1 (en) | 2015-12-03 |
AU2015271830A1 (en) | 2016-12-22 |
EP3148583A1 (en) | 2017-04-05 |
US20180339048A1 (en) | 2018-11-29 |
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