DE69837095T2 - Fluorierung von proteinen und peptiden für positronemissionstomographie - Google Patents
Fluorierung von proteinen und peptiden für positronemissionstomographie Download PDFInfo
- Publication number
- DE69837095T2 DE69837095T2 DE69837095T DE69837095T DE69837095T2 DE 69837095 T2 DE69837095 T2 DE 69837095T2 DE 69837095 T DE69837095 T DE 69837095T DE 69837095 T DE69837095 T DE 69837095T DE 69837095 T2 DE69837095 T2 DE 69837095T2
- Authority
- DE
- Germany
- Prior art keywords
- labeled peptide
- group
- peptide
- antibody
- use according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 108090000765 processed proteins & peptides Proteins 0.000 title claims abstract description 75
- 102000004196 processed proteins & peptides Human genes 0.000 title claims abstract description 22
- 102000004169 proteins and genes Human genes 0.000 title description 10
- 108090000623 proteins and genes Proteins 0.000 title description 10
- KRHYYFGTRYWZRS-BJUDXGSMSA-N ac1l2y5h Chemical compound [18FH] KRHYYFGTRYWZRS-BJUDXGSMSA-N 0.000 claims abstract description 83
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 34
- 238000002372 labelling Methods 0.000 claims abstract description 32
- 125000003396 thiol group Chemical class [H]S* 0.000 claims abstract description 27
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims abstract description 18
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims abstract description 18
- 238000002600 positron emission tomography Methods 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 31
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 12
- 150000003923 2,5-pyrrolediones Chemical group 0.000 claims description 11
- SPXOTSHWBDUUMT-UHFFFAOYSA-M 4-nitrobenzenesulfonate Chemical group [O-][N+](=O)C1=CC=C(S([O-])(=O)=O)C=C1 SPXOTSHWBDUUMT-UHFFFAOYSA-M 0.000 claims description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical group [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 11
- 150000001540 azides Chemical group 0.000 claims description 11
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical group I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 11
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical group [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 11
- 150000001336 alkenes Chemical class 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 6
- 150000003512 tertiary amines Chemical class 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 229910052751 metal Inorganic materials 0.000 claims description 5
- 239000002184 metal Substances 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- SBCXIPLNKGPIJQ-UHFFFAOYSA-N 4-hydroxy-2,5-dioxopyrrolidine-3-sulfonic acid Chemical compound OC1C(S(O)(=O)=O)C(=O)NC1=O SBCXIPLNKGPIJQ-UHFFFAOYSA-N 0.000 claims description 3
- 150000004697 chelate complex Chemical class 0.000 claims description 3
- 238000000163 radioactive labelling Methods 0.000 claims description 3
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000539 amino acid group Chemical group 0.000 claims description 2
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- BYKGZWMDFQXYHG-UHFFFAOYSA-N 2,5-dioxopyrrole-3-sulfonic acid Chemical compound OS(=O)(=O)C1=CC(=O)NC1=O BYKGZWMDFQXYHG-UHFFFAOYSA-N 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 24
- 239000013598 vector Substances 0.000 description 17
- 150000003573 thiols Chemical group 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 230000008685 targeting Effects 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 235000018102 proteins Nutrition 0.000 description 9
- -1 F-18 ion Chemical class 0.000 description 8
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000000269 nucleophilic effect Effects 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 5
- AUFVJZSDSXXFOI-UHFFFAOYSA-N 2.2.2-cryptand Chemical compound C1COCCOCCN2CCOCCOCCN1CCOCCOCC2 AUFVJZSDSXXFOI-UHFFFAOYSA-N 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
- 108010016076 Octreotide Proteins 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 229910052700 potassium Inorganic materials 0.000 description 4
- 239000011591 potassium Substances 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 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 description 3
- 229910052792 caesium Inorganic materials 0.000 description 3
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 239000012038 nucleophile Substances 0.000 description 3
- 229960002700 octreotide Drugs 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000007974 sodium acetate buffer Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- QMXCRMQIVATQMR-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-pyridin-2-ylsulfanylpropanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSC1=CC=CC=N1 QMXCRMQIVATQMR-UHFFFAOYSA-N 0.000 description 2
- ZLPORNPZJNRGCO-UHFFFAOYSA-N 3-methylpyrrole-2,5-dione Chemical compound CC1=CC(=O)NC1=O ZLPORNPZJNRGCO-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical group F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N iodoform Chemical compound IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- DPPDFTAXNOTIJG-UHFFFAOYSA-N 1-amino-3-[[1-(fluoromethyl)-9h-carbazol-4-yl]oxy]propan-2-ol Chemical compound N1C2=CC=CC=C2C2=C1C(CF)=CC=C2OCC(O)CN DPPDFTAXNOTIJG-UHFFFAOYSA-N 0.000 description 1
- WWHZZMHPRRFPGP-UHFFFAOYSA-N 2,2,2-triiodoacetic acid Chemical compound OC(=O)C(I)(I)I WWHZZMHPRRFPGP-UHFFFAOYSA-N 0.000 description 1
- SVTBMSDMJJWYQN-UHFFFAOYSA-N 2-methylpentane-2,4-diol Chemical compound CC(O)CC(C)(C)O SVTBMSDMJJWYQN-UHFFFAOYSA-N 0.000 description 1
- 102000012406 Carcinoembryonic Antigen Human genes 0.000 description 1
- 108010022366 Carcinoembryonic Antigen Proteins 0.000 description 1
- 229910020314 ClBr Inorganic materials 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- 229910006069 SO3H Inorganic materials 0.000 description 1
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 125000002228 disulfide group Chemical group 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 238000003682 fluorination reaction Methods 0.000 description 1
- RIHYOLCRHKZJPJ-UHFFFAOYSA-N fluoro(diiodo)methane Chemical compound FC(I)I RIHYOLCRHKZJPJ-UHFFFAOYSA-N 0.000 description 1
- VPLALCFPHOLSTP-UHFFFAOYSA-N fluoromethyl benzoate Chemical compound FCOC(=O)C1=CC=CC=C1 VPLALCFPHOLSTP-UHFFFAOYSA-N 0.000 description 1
- PREZBOFRYJAPOC-UHFFFAOYSA-N fluoromethylsulfanylmethylbenzene Chemical compound FCSCC1=CC=CC=C1 PREZBOFRYJAPOC-UHFFFAOYSA-N 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 238000002595 magnetic resonance imaging Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- IYYQIFHXKAKJPU-UHFFFAOYSA-N n-ethyl-n-(fluoromethyl)ethanamine Chemical compound CCN(CC)CF IYYQIFHXKAKJPU-UHFFFAOYSA-N 0.000 description 1
- 238000009206 nuclear medicine Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 150000004707 phenolate Chemical class 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
- CNHYKKNIIGEXAY-UHFFFAOYSA-N thiolan-2-imine Chemical compound N=C1CCCS1 CNHYKKNIIGEXAY-UHFFFAOYSA-N 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3007—Carcino-embryonic Antigens
-
- 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
- A61K51/083—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the peptide being octreotide or a somatostatin-receptor-binding 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
- A61K51/088—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
- A61K51/10—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
-
- 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
- C07B59/008—Peptides; Proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/13—Labelling of peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5748597P | 1997-09-03 | 1997-09-03 | |
| US57485P | 1997-09-03 | ||
| PCT/US1998/018268 WO1999011590A1 (en) | 1997-09-03 | 1998-09-03 | Fluorination of proteins and peptides for f-18 positron emission tomography |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69837095D1 DE69837095D1 (de) | 2007-03-29 |
| DE69837095T2 true DE69837095T2 (de) | 2007-11-22 |
Family
ID=22010853
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69837095T Expired - Lifetime DE69837095T2 (de) | 1997-09-03 | 1998-09-03 | Fluorierung von proteinen und peptiden für positronemissionstomographie |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US6187284B1 (enExample) |
| EP (1) | EP1009726B1 (enExample) |
| JP (1) | JP3992923B2 (enExample) |
| AT (1) | ATE353864T1 (enExample) |
| AU (1) | AU9375698A (enExample) |
| CA (1) | CA2302360C (enExample) |
| DE (1) | DE69837095T2 (enExample) |
| WO (1) | WO1999011590A1 (enExample) |
Families Citing this family (71)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6136311A (en) | 1996-05-06 | 2000-10-24 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
| US7387772B1 (en) * | 1999-06-22 | 2008-06-17 | Immunimedics, Inc. | Chimeric, human and humanized anti-CSAP monoclonal antibodies |
| WO1999066951A2 (en) * | 1998-06-22 | 1999-12-29 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
| US7138103B2 (en) * | 1998-06-22 | 2006-11-21 | Immunomedics, Inc. | Use of bi-specific antibodies for pre-targeting diagnosis and therapy |
| US7833528B2 (en) * | 1998-06-22 | 2010-11-16 | Immunomedics, Inc. | Use of multispecific, non-covalent complexes for targeted delivery of therapeutics |
| US6962702B2 (en) * | 1998-06-22 | 2005-11-08 | Immunomedics Inc. | Production and use of novel peptide-based agents for use with bi-specific antibodies |
| US7405320B2 (en) | 1998-06-22 | 2008-07-29 | Immunomedics, Inc. | Therapeutic and diagnostic conjugates for use with multispecific antibodies |
| US6998106B1 (en) * | 1998-12-01 | 2006-02-14 | Duke University | Radioconjugation of internalizing antibodies |
| DE10121741A1 (de) * | 2001-05-04 | 2002-11-14 | Forschungszentrum Juelich Gmbh | Verfahren zur Synthese trägerarmer ·18·F markierter Verbindungen |
| TWI266634B (en) * | 2002-02-06 | 2006-11-21 | Univ Johns Hopkins | Non-invasive diagnostic imaging technology for mitochondria dysfunction using radiolabeled lipophilic salts |
| US8877901B2 (en) | 2002-12-13 | 2014-11-04 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
| US7591994B2 (en) | 2002-12-13 | 2009-09-22 | Immunomedics, Inc. | Camptothecin-binding moiety conjugates |
| AU2003209886A1 (en) * | 2002-03-14 | 2003-09-22 | Qlt Inc. | Cancer associated araf1 protein kinase and its uses |
| GB0206750D0 (en) * | 2002-03-22 | 2002-05-01 | Amersham Plc | Radiofluorination methods |
| US7597876B2 (en) * | 2007-01-11 | 2009-10-06 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
| US7993626B2 (en) | 2007-01-11 | 2011-08-09 | Immunomedics, Inc. | Methods and compositions for F-18 labeling of proteins, peptides and other molecules |
| US7563433B2 (en) * | 2007-01-11 | 2009-07-21 | Immunomedics, Inc. | Methods and compositions for F-18 labeling of proteins, peptides and other molecules |
| FR2841558B1 (fr) * | 2002-07-01 | 2004-08-13 | Commissariat Energie Atomique | Peptides marques ayant une affinite pour un phospholipide et utilisations |
| FR2841554B1 (fr) * | 2002-07-01 | 2008-01-18 | Commissariat Energie Atomique | Composes de maleimides marques, leur procede de preparation et leur utilisation pour le marquage de macromolecules |
| US7189383B2 (en) * | 2002-08-02 | 2007-03-13 | Mallinckrodt Inc. | Radioactively labelled amino acid analogues, their preparation and use |
| US9701754B1 (en) | 2002-10-23 | 2017-07-11 | City Of Hope | Covalent disulfide-linked diabodies and uses thereof |
| GB0305704D0 (en) * | 2003-03-13 | 2003-04-16 | Amersham Plc | Radiofluorination methods |
| US7741524B2 (en) * | 2003-04-22 | 2010-06-22 | Solvay (Societe Anonyme) | Iodinated organic substances of low molecular mass and process for preparing them |
| CN1886362B (zh) | 2003-07-24 | 2010-10-13 | 皇后医学中心 | 烷基化剂的制备和用途 |
| US20050175534A1 (en) * | 2004-02-06 | 2005-08-11 | Adam Michael J. | Method of synthesizing compounds having a phosphorus-fluorine-18 bond |
| KR100808547B1 (ko) | 2005-06-22 | 2008-02-29 | 재단법인서울대학교산학협력재단 | 펩타이드 수용체 영상용 제제로 사용할 수 있는 ｆ－１８－플로로벤질리덴하이드라존－니코틴아마이드－펩타이드 유도체 및 펩타이드에 방사성불소를 효율적으로 표지하기 위한 방법 |
| US20070048803A1 (en) * | 2005-08-25 | 2007-03-01 | Lee Peter P | Immune profiling of lymph nodes associated with cancer |
| US20070092907A1 (en) * | 2005-10-21 | 2007-04-26 | Gambhir Sanjiv S | Methods of screening compound probes |
| GB0525949D0 (en) | 2005-12-21 | 2006-02-01 | Hammersmith Imanet Ltd | Pet radiotracers |
| ES2363891T3 (es) * | 2006-03-20 | 2011-08-18 | The Regents Of The University Of California | Anticuerpos contra el antígeno de células troncales de la próstata (psca) modificados genéticamente para el direccionamiento al cáncer. |
| US8889100B2 (en) | 2007-01-11 | 2014-11-18 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
| US8545809B2 (en) | 2007-01-11 | 2013-10-01 | Immunomedics, Inc. | Methods and compositions for improved 18F labeling of proteins, peptides and other molecules |
| US8709382B2 (en) | 2007-01-11 | 2014-04-29 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
| CA2675202C (en) * | 2007-01-11 | 2014-09-16 | Immunomedics, Inc. | Methods and compositions for improved f-18 labeling of proteins, peptides and other molecules |
| US8153100B2 (en) * | 2007-01-11 | 2012-04-10 | Immunomedics, Inc. | Methods and compositions for F-18 labeling of proteins, peptides and other molecules |
| US8398956B2 (en) | 2007-01-11 | 2013-03-19 | Immunomedics, Inc. | In vivo copper-free click chemistry for delivery of therapeutic and/or diagnostic agents |
| US8940298B2 (en) | 2007-09-04 | 2015-01-27 | The Regents Of The University Of California | High affinity anti-prostate stem cell antigen (PSCA) antibodies for cancer targeting and detection |
| US8029743B2 (en) * | 2007-09-19 | 2011-10-04 | General Electric Company | Microfluidic device with vertical injection aperture |
| CA2720037C (en) * | 2008-03-31 | 2016-08-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Purine derivatives as a3 adenosine receptor-selective agonists |
| US8916570B2 (en) | 2008-03-31 | 2014-12-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A3 adenosine receptor agonists and antagonists |
| AU2009276411B2 (en) * | 2008-08-01 | 2014-08-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A3 adenosine receptor antagonists and partial agonists |
| US9181253B2 (en) | 2008-08-01 | 2015-11-10 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Adenosine receptor agonists, partial agonists, and antagonists |
| US20100069616A1 (en) * | 2008-08-06 | 2010-03-18 | The Regents Of The University Of California | Engineered antibody-nanoparticle conjugates |
| US7927476B2 (en) * | 2008-12-22 | 2011-04-19 | General Electric Company | Injection method for microfluidic chips |
| PL3939617T3 (pl) | 2009-02-13 | 2025-03-17 | Immunomedics, Inc. | Związki pośrednie do wytwarzania koniugatów z wiązaniem rozszczepialnym wewnątrzkomórkowo |
| EP2398504B1 (en) | 2009-02-17 | 2018-11-28 | Cornell Research Foundation, Inc. | Methods and kits for diagnosis of cancer and prediction of therapeutic value |
| GB0905438D0 (en) * | 2009-03-30 | 2009-05-13 | Ge Healthcare Ltd | Radiolabelling reagents and methods |
| US8834839B2 (en) * | 2009-04-27 | 2014-09-16 | General Electric Company | Labeled molecular imaging agents, methods of making and methods of use |
| WO2011069019A2 (en) | 2009-12-02 | 2011-06-09 | David Ho | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (psma) and methods for their use |
| AU2010326004B2 (en) | 2009-12-04 | 2016-04-21 | Immunomedics, Inc. | Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules |
| JP6024025B2 (ja) | 2011-05-02 | 2016-11-09 | イミューノメディクス、インコーポレイテッドＩｍｍｕｎｏｍｅｄｉｃｓ， Ｉｎｃ． | 少容量投与用のアロタイプ選択抗体の限外濾過濃縮 |
| US8784774B2 (en) | 2011-09-16 | 2014-07-22 | General Electric Company | Labeled molecular imaging agents and methods of use |
| EP2861259A1 (en) | 2012-06-14 | 2015-04-22 | Ambrx, Inc. | Anti-psma antibodies conjugated to nuclear receptor ligand polypeptides |
| US8937186B2 (en) | 2012-08-21 | 2015-01-20 | Uop Llc | Acids removal and methane conversion process using a supersonic flow reactor |
| EP2774930A1 (en) | 2013-03-07 | 2014-09-10 | Aptenia S.R.L. | Metallocene compounds and labeled molecules comprising the same for in vivo imaging. |
| US9468692B2 (en) | 2014-01-23 | 2016-10-18 | General Electric Company | Labeled molecular imaging agents and methods of use |
| US9468693B2 (en) | 2014-01-23 | 2016-10-18 | General Electric Company | Labeled molecular imaging agents and methods of use |
| EP3110445A4 (en) | 2014-02-25 | 2017-09-27 | Immunomedics, Inc. | Humanized rfb4 anti-cd22 antibody |
| US11229713B2 (en) | 2014-11-25 | 2022-01-25 | Bristol-Myers Squibb Company | Methods and compositions for 18F-radiolabeling of biologics |
| WO2016130549A1 (en) * | 2015-02-09 | 2016-08-18 | The Trustees Of Princeton University | Targeted, metal-catalyzed fluorination of complex compounds with fluoride ion via decarboxylation |
| EP3286224A4 (en) | 2015-04-22 | 2018-11-14 | Immunomedics, Inc. | Isolation, detection, diagnosis and/or characterization of circulating trop-2-positive cancer cells |
| NZ739721A (en) | 2015-08-07 | 2019-09-27 | Imaginab Inc | Antigen binding constructs to target molecules |
| EA038019B1 (ru) | 2016-05-19 | 2021-06-23 | Бристол-Маерс Сквибб Компани | Иммуномодуляторы для пэт-визуализации |
| US10994033B2 (en) | 2016-06-01 | 2021-05-04 | Bristol-Myers Squibb Company | Imaging methods using 18F-radiolabeled biologics |
| US11266745B2 (en) | 2017-02-08 | 2022-03-08 | Imaginab, Inc. | Extension sequences for diabodies |
| JP7366755B2 (ja) | 2017-05-30 | 2023-10-23 | ザ ボード オブ リージェンツ オブ ザ ユニヴァーシティ オブ オクラホマ | 抗ダブルコルチン様キナーゼ１抗体および使用方法 |
| WO2019227490A1 (en) | 2018-06-01 | 2019-12-05 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and methods for imaging |
| US11987629B2 (en) | 2018-06-01 | 2024-05-21 | Tayu Huaxia Biotech Medical Group Co., Ltd. | Compositions and uses thereof for treating disease or condition |
| CN113795511B (zh) | 2019-01-23 | 2024-07-23 | 大有华夏生物医药集团有限公司 | 抗pd-l1双抗体及其用途 |
| WO2022265912A1 (en) | 2021-06-16 | 2022-12-22 | Gundersen Lutheran Medical Foundation, Inc. | Antibodies targeting an amphiregulin-derived cell surface neo-epitope |
| CN115231995A (zh) * | 2022-06-14 | 2022-10-25 | 上海应用技术大学 | 一种单氟二溴代丙酮衍生物及其制备与应用 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998016254A1 (en) * | 1996-10-17 | 1998-04-23 | Immunomedics, Inc. | Non-antigenic toxin-conjugate and fusion protein of internalizing receptor system |
-
1998
- 1998-09-03 JP JP2000508634A patent/JP3992923B2/ja not_active Expired - Fee Related
- 1998-09-03 US US09/146,318 patent/US6187284B1/en not_active Expired - Lifetime
- 1998-09-03 AU AU93756/98A patent/AU9375698A/en not_active Abandoned
- 1998-09-03 DE DE69837095T patent/DE69837095T2/de not_active Expired - Lifetime
- 1998-09-03 WO PCT/US1998/018268 patent/WO1999011590A1/en not_active Ceased
- 1998-09-03 EP EP98946820A patent/EP1009726B1/en not_active Expired - Lifetime
- 1998-09-03 CA CA002302360A patent/CA2302360C/en not_active Expired - Lifetime
- 1998-09-03 AT AT98946820T patent/ATE353864T1/de not_active IP Right Cessation
-
2000
- 2000-08-24 US US09/644,706 patent/US6358489B1/en not_active Expired - Lifetime
-
2002
- 2002-02-11 US US10/071,247 patent/US6953567B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US6953567B2 (en) | 2005-10-11 |
| WO1999011590A1 (en) | 1999-03-11 |
| CA2302360A1 (en) | 1999-03-11 |
| EP1009726A1 (en) | 2000-06-21 |
| JP3992923B2 (ja) | 2007-10-17 |
| DE69837095D1 (de) | 2007-03-29 |
| US6187284B1 (en) | 2001-02-13 |
| JP2001515843A (ja) | 2001-09-25 |
| AU9375698A (en) | 1999-03-22 |
| ATE353864T1 (de) | 2007-03-15 |
| US6358489B1 (en) | 2002-03-19 |
| US20020119096A1 (en) | 2002-08-29 |
| CA2302360C (en) | 2005-11-15 |
| EP1009726B1 (en) | 2007-02-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69837095T2 (de) | Fluorierung von proteinen und peptiden für positronemissionstomographie | |
| DE3889956T2 (de) | Metall-Radionuklid-markierte Proteine und Glykoproteine zur Diagnose und Therapie. | |
| DE69230525T2 (de) | Technetium-99m markierte Polypeptide zur Bildformung | |
| DE69309479T2 (de) | Markiertes monocyte-chemoattractant-proteinmaterial und medizinische anwendung | |
| DE69126124T2 (de) | Polymere träger zur freisetzung kovalent gebundener wirkstoffe | |
| DE68908273T2 (de) | Metal Radionukleid-Chelatverbindungen mit verbesserter Chelatierungskinetik. | |
| JP2001515843A5 (enExample) | ||
| DE69803205T2 (de) | Verfahren zur herstellung von facial metall tricarbonyl verbindungen und ihre anwendung zur markierung von biosubstraten | |
| DE69529084T2 (de) | Modifiziertes radio-antikörper fragment zur reduzierten renalen aufnahme | |
| DE69315565T2 (de) | Konjugate von biotin und deferoxamine für radio-immuntherapie und -immunbilderzeugung | |
| DE69531502T2 (de) | Monoamid, diamid, thiol enthaltende metall-chelatierende verbindungen | |
| DE69030025T2 (de) | Verfahren zur Markierung von Proteinen mit Technetium/Rhenium | |
| DE69310733T2 (de) | Technetium-99m-markierte peptide zur bilderzeugung | |
| DE3751890T2 (de) | Radionuklid-Antikörper-Verbindung | |
| DE3850497T2 (de) | Methode zur markierung von antikörpern mit einem metallion. | |
| DE69520256T2 (de) | Chelatbildende Gruppen enthaltende Somastotatin-Analoge und deren radiomarkierteZusammensetzungen | |
| DE69819478T2 (de) | Verfahren zum Nachweis und zur Lokalisierung maligner menschlicher Pankreastumore | |
| DE69231324T2 (de) | Chelatbildende Gruppen enthaltende Somatostatin Analoge und deren radiomarkierten Zusammensetzungen | |
| DE69837038T2 (de) | Tetraaza- oder n2s2-komplexanten, und deren verwendung in der radiodiagnostik oder radiotherapie | |
| DE69131850T2 (de) | Technetium-99m-komplexe zur verwendung als radiopharmazeutische mittel | |
| DE69231952T2 (de) | Komplexbildnermittel und zielimmunoreagenzien | |
| DE68919366T2 (de) | Spaltbare linker zur reduzierung der akkumulierung von immunokonjugaten in nicht-zielorganen. | |
| DE69230287T2 (de) | Verbindungen und pharmazeutische zusammensetzungen zum nachweis und zur lokalisierung von geweben mit neurokinin-1-rezeptoren | |
| DE69022542T2 (de) | Chelatierungsmittel zur bindung von metallionen zu proteinen. | |
| DE69026387T2 (de) | Reduktion der nichtzielspezifischen retention von immunokonjugaten und ihren metaboliten |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |