WO2010092114A1 - Use of buffers for radionuclide complexation - Google Patents
Use of buffers for radionuclide complexation Download PDFInfo
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- WO2010092114A1 WO2010092114A1 PCT/EP2010/051709 EP2010051709W WO2010092114A1 WO 2010092114 A1 WO2010092114 A1 WO 2010092114A1 EP 2010051709 W EP2010051709 W EP 2010051709W WO 2010092114 A1 WO2010092114 A1 WO 2010092114A1
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- WIPO (PCT)
- Prior art keywords
- chelate
- vectorized
- buffer
- advantageously
- solution
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- C—CHEMISTRY; METALLURGY
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
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- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
Definitions
- the invention relates to improved compositions of contrast agents and to a method for preparing such compositions.
- the invention relates in particular to products for PET (positron emission tomography) imaging, and especially products containing a radionuclide for PET imaging, preferably gallium 68.
- Document WO 2007/042504 in the name of the applicant explains in detail the advantage of PET imaging, in particular with gallium 68 (Ga68) which is very advantageous since it does not require the use, in the vicinity of or within the hospital, of a very bulky and expensive cyclotron.
- the Ga68 produced by a small dedicated generator is coupled to a "vectorized chelate" (referred to without distinction as “cold kit” in the present application) which is not yet labeled, the coordination reaction (complexing of the radionuclide by the cold kit) providing a Ga68-"radiolabeled vectorized chelate” (referred to without distinction as “complexed vectorized chelate” in the present application), which is administered to the patient for PET imaging.
- a vectorized chelate referred to without distinction as “cold kit” in the present application
- the coordination reaction complexing of the radionuclide by the cold kit
- a Ga68-"radiolabeled vectorized chelate referred to without distinction as “complexed vectorized chelate” in the present application
- the vectorized chelate comprises "a targeting part” (referred to without distinction as “targeting agent” or “biovector” in the present application) for targeting a specific biological target (cell receptor, for example), in particular a pathological region of diagnostic interest, said targeting part being linked, typically by a chemical linker (covalent bond via any appropriate bonding group) to the chelate constituting the signal part.
- a targeting part for targeting a specific biological target (cell receptor, for example), in particular a pathological region of diagnostic interest
- This chelate is capable of complexing the radionuclide (for example, a macrocyclic chelate such as DOTA, NOTA or PCTA).
- the solution of radioactive Ga68, the gallium-generator eluate is mixed, in a dedicated and protected area of the hospital (area denoted radiopharmacy), with a vectorized-chelate solution prepared in advance (the cold kit), provided by the manufacturer of the contrast product.
- the mixing is carried out in an automated device into which are introduced, on the one hand, the dose of generator-eluate Ga68 and, on the other hand, the dose of vectorized chelate (not yet radiolabeled with Ga68).
- the intention is always to improve the conditions for preparing the radiolabeled contrast agent, and in particular to obtain a very rapid and simple complexation with a high degree of purity of the radiolabeled chelate. More specifically, the intention is to obtain a complexation in a very short time, with a yield and a purity for the radiolabeled chelate of at least 90%, preferably of at least 95%.
- the prior art first of all described gallium complexation carried out by heating at a temperature of the order of 75 0 C to 95°C, for at least 15 minutes. A satisfactory degree of purity was achieved at these temperatures using HEPES (sulfonic acid derivative) or acetate buffers.
- HEPES sulfonic acid derivative
- acetate buffers for gallium technology, the prior art first of all described gallium complexation carried out by heating at a temperature of the order of 75 0 C to 95°C, for at least 15 minutes. A satisfactory degree of purity was achieved at these temperatures using HEPES (sulfonic acid derivative) or acetate buffers.
- this heating time is, on the other hand, relatively long compared with the short life of the Gallium68 isotope, and requires appropriate equipment.
- the buffer used may no longer have the required buffering capacity, which may disrupt the complexation and/or impair the bio vector, and thus mean that the product does not comply with the specifications that it has to meet in order to be injected into the patient; - the HEPES buffer does not appear in the pharmacopea, thereby posing complex pharmaceutical regulation problems in terms of clinical use in humans.
- the prior-art research did not relate to the buffer solutions that can be used, but to the method of heating or the need for such heating.
- the HEPES buffer is described as effective at a pH of 4.6-4.8 and 1 M
- the acetate buffer is described as effective at a pH of 4.6-4.8 and 0.4 M.
- complexation in particular at ambient temperature, with neither a heating step nor microwaves, is obtained successfully, in particular in terms of the rapidity of complexation (in less than 15 minutes, preferably in less than 10 minutes, more preferably in 3 to 10 minutes, for example 5 to 8 minutes) and of the quality of the radiolabeled chelates, through the use, for the complexation reaction, of certain appropriate buffers of the pharmacopea other than HEPES and acetate, under physicochemical complexation conditions (in particular concentrations and pH) that are less strict and limiting than in the prior art.
- the buffers of the applicant enable satisfactory complexation, with a suitable degree of complexation, advantageously at least 92%, 95%, 97%, and a sufficient purity (at least 92%, 95%, 97%) and preferably without the formation of precipitate to be eliminated. More specifically, the applicant has obtained very advantageous results with the buffers comprising at least two Gallium 68-coordination functions described below and as described in the detailed examples.
- the invention relates to a method for complexation (referred to without distinction as "method of radio labeling" in the present application) of a chelate with a radionuclide, advantageously gallium, the complexation being carried out, advantageously at ambient temperature without heating, by adding the radionuclide to the chelate in a buffer solution, the buffer of this solution comprising between two and five functions for coordination with the radionuclide, each coordination function being independently chosen from a carboxylic acid function and a hydroxyl function, on the condition that the buffer comprises at least one carboxylic acid function and at most two carboxylic acid functions.
- the applicant has made a judicious choice of the buffers in such a way that the complexation kinetics are sufficiently rapid to allow varied and flexible conditions for use (in particular pH and heating conditions).
- carboxylic acid coordination function is intended to mean any carboxylic acid function COOH and the functions that are equivalent to COOH from the point of view of Ga68 complexation, and in particular: an acid function included in a ring, for instance having the following
- the isoteric functional group for example PO3H2 (as demonstrated with phosphoric acid in particular).
- the function sulfonic acid is excluded from the definition of carboxylic acid function.
- the invention covers the case of a poly acid/base function having several pKa of between 2 and 13, associated with the same functional group (the case of the phosphoric acid buffer in particular).
- the complexation is even better when, in the case where the buffer contains two carboxylic acid functions, it also contains at least one hydroxyl function (better complexation without the need to filter off precipitate after the complexation).
- the invention relates to a method of radio labeling characterized in that the buffer also comprises a hydroxyl function.
- the buffers used advantageously comprise two carboxylic acid functions and at least one hydroxyl function, and in particular one or two hydroxyl functions.
- the buffers used advantageously comprise at least one carboxylic acid function and at least one hydroxyl function.
- the buffer is chosen from the following buffers: lactate, tartrate, malate, maleate, succinate, ascorbate, carbonate and phosphate, and mixtures thereof.
- the buffer is a C 1 -C 10 monocarboxylic acid which is monohydroxylated, optionally di-, tri- or tetrahydroxylated, and optionally unsaturated (in particular having at least one double bond), or a C 1 -C 10 dicarboxylic acid which is optionally mono-, di- or trihydroxylated, and optionally unsaturated (in particular having at least one double bond).
- the buffer is chosen from the following buffers: lactate, tartrate and malate, or mixtures thereof.
- - tartrate has two carboxylic acid functions and two hydroxyl functions
- - lactate has one carboxylic acid function and one hydroxyl function.
- HEPES and acetic acid comprise, respectively, zero and a single carboxylic acid function.
- Table 1 recalls the formulae of the buffers which are not comprised within the claimed invention.
- the pH of the solution for complexation using the buffers of the invention is advantageously between 1 and 14, typically between 3 and 11, advantageously between 3 and 7.
- the buffering capacity is the pKa value +/- 1, which means, for example, 3.75-5.75 for acetate.
- the range is much broader, for example [2.04-5.37] for tartrate, [5.35-11.33] for carbonate and [1.12-13.67] for phosphate.
- NOTA is particularly advantageous for lactate, carbonate or tartrate buffers.
- acetate which contains just one function, would not be sufficiently complexing to be effective for varied complexation conditions (concentration, pH); HEPES which contains one sulfonate function and one hydroxyl group, would also not be sufficiently complexing;
- the invention concerns the case of buffers such that the log K Ga68 value is between 3 and 6, preferably between 3 and 5.
- the applicant has realized that the constant for Ga68 complexation by the buffer (log K Ga68 of the buffer comprising between 2 and 4 coordination functions) is very advantageously between 2 and 6, and very advantageously between 3 and 5, preferably of the order of 4 (between 3.5 and 4.5 in particular).
- the buffer is a combination of at least two of the buffers indicated above, for example a mixture of lactate and tartrate buffer. All combinations are possible with, for example, the following proportions between the buffers of the present invention: 90/10, 80/20, 60/40, 50/50 for two buffers, and 80/10/10, 60/20/20 for three buffers.
- a mixture, for example, of a lactate-type buffer according to the invention very effective for a given chelate and a buffer less effective for this chelate could also be used.
- a mixture of very effective buffer according to the invention (lactate, for example), with a buffer that is not effective alone (citrate, in particular), but on the condition of using a sufficiently small proportion of the buffer that is not effective alone so as not to impair the complexation.
- the chelate that can be used in the context of the present invention is a free (i.e. nonvectorized) chelate or a vectorized chelate, the chelate being capable of complexing the radionuclide.
- it is a vectorized chelate.
- the term "vectorized chelate” is intended to mean any chelate to which is bound (by means of a chemical linker) a part for targeting a specific biological target, in particular a region of diagnostic interest.
- the chelate is vectorized with an agent for targeting a specific biological target, in particular a region of diagnostic interest.
- the chelate part of the vectorized chelate is well known to those skilled in the art, and it is preferably one of the chelates preferred for the complexation of Ga68, such as NOTA and its derivatives, PCTA and its derivatives, AAZTA and its derivatives.
- the vectorized chelate is advantageously chosen from vectorized NOTA, vectorized PCTA, vectorized DOTA, vectorized AAZTA, advantageously dideaza-NOTA, dideaza PCTA, folate NOTA, folate PCTA folate AAZTA.
- a lactic, tartaric or carbonic buffer for NOTA a lactic or carbonic buffer for PCTA.
- a large number of chelates can be used, in particular a) a macrocyclic chelate having the general formula below:
- M-M1-M2 forms a pyridine nucleus, or Ml and M2 are absent and M represents a bond, or M is N-R and Ml and M2 represent a hydrogen atom or a methyl, with R being chosen independently from CH 2 CO 2 - or H or CHX-CO 2 -, with at least one R being CHXCO 2 - and X being L(Linker)-B (Biovector);
- a linear chelate notably a linear chelate chosen from: EDTA, DTPA diethylenetriaminopentaacetic acid, N-[2-[bis(carboxymethyl)amino]-3-(4- ethoxyphenyl)propyl] -N- [2- [bis(carboxymethyl)amino] ethyl] -L-glycine (EOB-DTPA), N,N-bis[2-[bis(carboxymethyl)amino]ethyl]-L-glutamic acid (DTPA-GLU),
- Use may in particular be made of a macrocyclic chelate from 1,4,7,10- tetraazacyclododecane-l,4,7,10-tetraacetic acid (DOTA), 1,4,7,10- tetraazacyclododecane-l,4,7-triacetic acid (D03A), 10-(2-hydroxypropyl)- l,4,7,10-tetraazacyclododecane-l,4,7-triacetic acid (HPDO3A), 2-methyl- l,4,7,10-tetraazacyclododecane-l,4,7,10-tetraacetic acid (MCTA), (alpha, alpha ', alpha ", alpha '”)-tetramethyl-l, 4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTMA) and 3,6,9,15- tetraazabicyclo[9.3.1]pentadeca-l
- Use may also be made of a chelate from: HOPO and derivatives known, AAZTA, DOTA gadofluorines, D03A, HPDO3A, TETA, TRITA, HETA, DOTA-NHS, M4D0TA, M4DO3A, PCTA and their 2-benzyl-DOTA-alpha- (2-phenethyl)- 1,4,7,10-tetraazacyclododecan- 1 -acetic-4,7, 10-tris(methylacetic) acid, 2-benzyl-cyclohexyldiethylenetriaminepentaacetic acid, 2-benzyl-6- methyl-DTPA, 6,6"-bis [N, N, N", N"tetra(carboxymethyl)aminomethyl)-4'-(3- amino-4-methoxyphenyl)- 2,2': 6', 2"-terpyridine, N,N'-bis(pyridoxal-5- phosphate) ethylenediamine- N, N'-di
- NOTA compounds which are denoted C- functionalized (at least one group Y grafted onto a carbon atom of the NOTA enables the coupling of the biovector) and NOTA compounds carrying at least one additional CH 2 group in the ring.
- it is the NOTA derivative of formula
- Use may also be made of NOTA derivatives, NODA derivatives, NODA-GA. Use may also be made of the following chelates:
- Dff-LICAM chelates or derivatives for which the presence of the sulfonic acid function may cause the excretion to change toward the kidneys rather than toward the liver.
- Use may also be made, in general, of any chelate capable of forming a sufficiently stable cage around Ga 3+ , in particular any aliphatic, macrocyclic or linear amine, or macrocycle amine with tertiary amines.
- the vectorized-chelate-targeting part is a biovector for targeting a pathological region of diagnostic interest, the biovector being advantageously an amino acid, a peptide, advantageously comprising 4 to 15, or 4 to 10 amino acids, a polypeptide, a vitamin, a monosaccharide or polysaccharide, an antibody, a nucleic acid, a bicyclam or an aptamer.
- biovector targeting cell receptors in particular all the receptors described below
- a pharmacophore organic molecule with pharmacological activity
- an angiogenesis-targeting biovector an MMP -targeting biovector
- a tyrosine-kinase-targeting peptide an atheroma-plaque-targeting peptide or an amyloid-plaque-targeting biovector
- a VCAM targeting biovector peptidic or non peptidic.
- the biovector(s) is (are), for example, chosen from the following list (the documents and references between parentheses are examples and not a limiting list): 1) Bio vectors targeting angiopoietin and VEGF receptors (described in WO 01/97850), polymers such as polyhistidine (US 6,372,194), fibrin- targeting polypeptides (WO 2001/9188), integrin-targeting peptides (WO 01/77145, WO 02/26776 for ccv ⁇ 3, WO 02/081497, for example RGDWXE), pseudopeptides and peptides for targeting metalloproteases MMP (WO 03/062198, WO 01/60416), peptides targeting, for example, the KDR/Flk-1 receptor or Tie-1 and 2 receptors (WO 99/40947, for example), sialyl Lewis glycosides (WO 02/062810 and M ⁇ ller et al, Eur.
- antioxidants such as ascorbic acid (WO 02/40060), tuftsin-targeting biovectors (for example, US 6,524,554), biovectors for targeting G protein receptors, GPCRs, in particular cholecystokinin (WO 02/094873), associations between an integrin antagonist and a guanidine mimic (US 6 489 333), ⁇ v ⁇ 3 -targeting or ⁇ v ⁇ 5 -targeting quinolones (US 6,511,648), benzodiazepines and analogs targeting integrins (US A 2002/0106325, WO 01/97861), imidazoles and analogs (WO 01/98294), RGD peptides (WO 01/10450), antibodies or antibody fragments (FGF, TGF ⁇ , GV39, GV97, ELAM, VCAM, which are TNF- or IL-inducible (US 6,261,535)), targeting molecules which are modified by interaction with
- Angiogenesis inhibitors in particular those tested in clinical trials or already marketed, in particular: - inhibitors of angiogenesis involving FGFR or VEGFR receptors, such as SUlOl, SU5416, SU6668, ZD4190, PTK787, ZK225846, azacyclic compounds (WO 00244156, WO 02059110);
- BB25-16 marimastat
- AG3340 prinomastat
- solimastat BAY12-9566
- BMS275291 metastat
- metastat metastat
- - inhibitors of angiogenesis involving integrins such as SM256, SG545, adhesion molecules which block EC-ECM (such as EMD 121-974, or vitaxin); - medicaments with a more indirect mechanism of antiangiogenic action, such as carboxyamidotriazole, TNP470, squalamine, ZDOlOl;
- VEGF-targeting biovectors described in Nuclear Medicine Communications, 1999, 20;
- Biovectors capable of targeting receptors CD36, EPAS-I, ARNT, NHE3, Tie-1, 1/KDR, FIt-I, Tek, neuropilin-1, endoglin, pleiotropin, endosialin, AxL, alPi, a2ssl, a4Pl, a5pl, eph B4 (ephrin), the laminin A receptor, the neutrophilin receptor 65, the leptin receptor OB-RP, the chemokine receptor CXCR-4 (and other receptors mentioned in document WO 99/40947), bombesin/GRP, receptors for gastrin, VIP, CCK. 4) Biovectors of tyrosine kinase inhibitor type.
- GPIIb/IIIa receptor inhibitors chosen from: (1) the fab fragment of a monoclonal antibody against the GPIIb/IIIa receptor, Abciximab, (2) small peptide and peptidomimetic molecules injected intravenously, such as eptif ⁇ batide and tirofiban. 6) Fibrinogen receptor antagonist peptides (EP 425 212), Ilb/IIIa receptor ligand peptides, fibrinogen ligands, thrombin ligands, peptides capable of targeting atheroma plaque, platelets, fibrin, hirudin-based peptides, guanine-based derivatives targeting the Ilb/IIIa receptor.
- biovectors or biologically active fragments of bio vectors known to those skilled in the art as medicaments, having an anti-thrombotic, anti-platelet-aggregation, anti-atherosclerotic, anti-restenoic or anticoagulant action.
- biovectors or biologically active fragments of biovectors targeting ccv ⁇ 3, described in association with DOTAs in patent US 6 537 520 chosen from the following: mitomycin, tretinoin, ribomustin, gemcitabine, vincristine, etoposide, cladribine, mitobronitol, methotrexate, doxorubicin, carboquone, pentostatin, nitracrine, zinostatin, cetrorelix, letrozole, raltitrexed, daunorubicin, fadrozole, fotemustine, thymalfasin, sobuzoxane, nedaplatin, cytarabine, bicalutamide, vinorelbine, vesnarinone, aminoglutethimide, amsacrine, proglumide, elliptinium acetate, ketanserin, doxiflur
- biovectors for targeting P-selectin, E-selectin for example, the 8-amino-acid peptide described by Morikawa et al, 1996, 951, and also vanous sugars.
- Any peptide obtained by targeting technologies such as phage display, optionally modified with unnatural amino acids (http//chemlibrary.bri.nrc.ca), for example peptides derived from phage display libraries: RGD, NGR, KGD, RGD-4C.
- Vitamins in particular folic acid and its known derivatives capable of targeting fo late receptors .
- Biovectors targeting kinases for example tyrosine kinases.
- - biovectors for targeting peptide receptors overexpressed in tumors LHRH receptors, bombesin/GRP, VIP receptors, CCK receptors, tachykinin receptors, for example
- LHRH receptors LHRH receptors, bombesin/GRP, VIP receptors, CCK receptors, tachykinin receptors, for example
- analogs of somatostatin or of bombesin optionally glycosylated octreotide peptide derivatives, VIP peptides, alpha-MSHs, CCK-
- Myocardial viability markers for example, tetrofosmin and hexakis(2-methoxy-2-methylpropylisonitrile)).
- Fibrin-binding peptides in particular the peptide sequences described in WO 03/11115.
- Amyloid plaque aggregation inhibitors described in WO 02/085903 for example.
- Compounds for targeting Alzheimer's disease in particular compounds comprising backbones of benzothiazole, benzofuran, styrylbenzoxazole/thiazole/imidazole/quinoline, styrylpyridine type, and known derivatives thereof.
- the biovector is an agent for targeting chemokine receptors, and in particular for targeting CXCR4.
- bicyclams for example, all the derivatives described in WO2006032704
- peptides in particular cyclic peptides
- peptides in particular peptides of 3 to 10 amino acids, preferably 3 to 8 amino acids, for example 4 to 6 amino acids.
- use will be made of a peptide among the following: a) Cyclo(D-Tyr-X-Arg-Nal-Gly)
- the biovector is a folate-receptor- targeting biovector, such as a folic acid or any known derivative of folic acid,0 and in particular a derivative having the formula in document WO2004112839 (El):
- Rf 2 alkyl C ⁇ CH)-, Ci-Ci 2 alkyl and Ci-Ci 2 alkoxy; in which Zf is O or S; preferably, Kl is -N(Rf4")- or -C(Rf ⁇ ")(R f 7")- with Rf4", Rf ⁇ " and R f 7" being H; A2 optionally being covalently bonded to an amino acid; i) R f 2, R f 3, Rf4, Rf4', Rf4", R f 5, R f 5'", Rf6" and R f 7" are chosen independently from the group constituted of: H, halo, Ci-Ci 2 alkyl, Ci-Ci 2 alkoxy, Ci-Ci 2 alkanoyl, C 2 -Ci 2 alkenyl, C 2 -Ci 2 alcynyl, (Ci-Ci 2 alkoxy)carbonyl, and (C, -C, 2 alkylamino) carbonyl; h
- RfI, R f 2, R f 3, Rf4, Rf4', Rf4", R f 5, R f 5", Rf ⁇ , R f 7", Rf ⁇ , R f 7, Rf ⁇ ' and R f 7' comprises an alkyl, alkoxy, alkylamino, alkanoyl, alkenyl, alkynyl, alkoxycarbonyl or alkylaminocarbonyl group, the group preferably contains 1 to 6 carbon atoms (Ci-C 6 ), more preferably 1 to 4 carbon atoms (C1-C4).
- the inventors have in particular focused on the derivatives a)
- the biovector is a folate or a folate derivative.
- the folate derivatives thus include the following compounds: pteropolyglutamic acid, pteridines capable of targeting the folate receptor (tetrahydropterins, tetrahydrofolates, dihydro folates in particular).
- the folate derivatives also include the following compounds: aminopterin, amethopterin (methotrexate), N-methylfolate, 2-deaminohydroxyfolate; and deaza derivatives thereof such as 1-deazamethopterin or 3-deazamethopterin, and 3',5'-dichloro-4-amino-4-deoxy-N-methylpteroylglutamic acid (dichloromethotrexate) .
- the folate derivatives include the deaza or dideaza compounds.
- the terms "deaza” and “dideaza” refer to the known derivatives, which do not have nitrogen atoms G3, G5, G6 of folic acid.
- the deaza derivatives include the 1 -deaza, 3-deaza, 5-deaza, 8-deaza and 10-deaza derivatives.
- Patents WO2007042504 and WO2004112839 (incorporated by way of reference) by the applicant illustrate numerous examples of chemical coupling between various bio vectors and various chelates, typically by means of chemical linkers. By way of examples, mention will be made of the following linkers: 1) amino acids.
- linkers L capable of interacting with at least one biovector functional group and at least one chelate functional group.
- L includes in particular alkyl chains which are substituted or unsubstituted, saturated or unsaturated, and straight or branched, peptides, polyethylene glycols and polyoxy ethylenes. Mention will in particular be made of:
- Pl and P2 are thus groups for coupling the linker with, on the one hand, the chelate and, on the other hand, the biovector.
- linkers described in patent US 6 264 914 capable of reacting with amino, hydroxyl, sulfhydryl, carboxyl, carbonyl, carbohydrate, thioether, 2- aminoalcohol, 2-aminothiol, guanidinyl, imidazolyl and phenolic functional groups (of the biovector and of the chelate); and with the definition summaries of WO 2007/042504.
- linkers described in document WO 02/085908 for example a linear or branched chain of a linker, chosen from:
- linkers structure and size
- the choice of the linkers may be made in particular in such a way as to control in particular the charge, the lipophilicity and/or the hydrophilicity of the product as a function of the desired diagnostic indication, so as to optimize the biological targeting and/or the biodistribution.
- Linkers which are biodegradable in vivo, PEG linkers or mini-PEG linkers may in particular be used.
- the products vectorized and radiolabeled, and solubilized in a buffer solution using the buffers of the applicant form gallium metal complexes of formula: .biovector
- the buffers used are typically under the form of a buffer solution comprising at least a conter-ion, in particular sodium or ammoniumor an ion of an organic base (advantageously an organic polybase such as meglumine, ethylenediamine, diethylenetriamine, tetramethylethylenediamine, triethylenetetramine).
- an organic polybase such as meglumine, ethylenediamine, diethylenetriamine, tetramethylethylenediamine, triethylenetetramine.
- the lactate buffer is used as sodium lactate or ammonium lactate, for which the applicant has shown the efficiency.
- the invention also relates to a method for preparing a radiolabeled contrast product, comprising the following steps:
- a buffer solution according to the present invention advantageously at ambient temperature without heating and without microwaves, in less than 15 minutes, preferably in less than 10 minutes, more preferably in less than 7 minutes, the solution of radionuclide and of the vectorized chelate.
- the buffer is chosen from: lactate, tartrate, malate, succinate, maleate, ascorbate, carbonate and phosphate buffers, and mixtures thereof, even more advantageously from lactate, tartrate and carbonate buffers, and mixtures thereof.
- the vectorized chelate (not yet radio labelled) is provided in the form of a concentrated aqueous solution, before the introduction of the buffer solution, and the acid eluate (pH around 2) of Ga68.
- a volume of 0.4 ml of 0.6 nM Ga68 solution is added to the reactor which contains 1 ml of buffer solution and 20 ⁇ l of 1.2 M vectorized chelate solution.
- a greater amount of Ga68 solution at an appropriate dilution may be provided.
- the labeled chelate is provided in buffer solution and not in an aqueous solution different than the buffer.
- the invention also relates to the various intermediate products where appropriate required for the complexation in the buffer solutions of the invention, and in particular: - an eluate of Ga68 (the eluate being produced by a Ga68 generator) in solution in 98% of acetone, 0.05M HcI
- a buffer solution chosen from the buffers of the present application advantageously lactic, tartaric, succinic, ascorbic, phosphoric, and carbonic buffers, and combinations thereof
- a vectorized chelate, not yet complexed with the Ga68 radionuclide in buffer solution or in water, the buffer being chosen from the buffers of the present application, advantageously lactic, tartaric, succinic, ascorbic, phosphoric and carbonic buffers, and combinations thereof.
- a combination of buffers can also be used as complexation buffer solution, in particular a combination of at least two buffers mentioned above, for example a mixed lactic-succinic or lactic-tartaric buffer, in proportions of advantageously 90/10, 80/20, 70/30, 60/40, 50/50 for combinations of two buffers.
- the invention relates to an injectable solution comprising a buffer and a chelate complexed with a radionuclide, the buffer comprising between two and five functions for coordination with the radionuclide, each coordination function being independently chosen from a carboxylic acid function and a hydroxyl function, on the condition that the buffer comprises at least one carboxylic acid function and at most two carboxylic acid functions.
- the buffer solution is a solution at from 0.05 to 1.5 M with respect to buffer, preferably from 0.1M to IM with respect to buffer ; advantageously 0.1 to 0.5 M, for instance 0.1 to 0.3 M.
- the concentration of the radiolabeled vectorized chelate in the injectable buffer solution is between 0.1 and 100 ⁇ M, for example 0.5 to 20 ⁇ M, in particular 1 to 10 ⁇ M.
- the solution administered to the patient also comprises at least one excipient that is suitable for limiting radiolysis, i.e. decomposition of the diagnostic compound administered.
- excipient that is suitable for limiting radiolysis, i.e. decomposition of the diagnostic compound administered.
- Antiradio lysis agents are known to those skilled in the art and summarized in particular in WO2007042504 and W02005009393 (examples: free-radical blockers, dithiocarbamates, PDTC, soluble selenium compounds such as selenomethionine or selenocystine with, where appropriate, sodium ascorbate, derivatives capable of reducing oxidized amino acids, such as methionine, in particular thiol derivatives of cysteine, mercaptoethanol, dithiothreitol). Arginine or lysine formulations may also be used.
- the applicant's products in buffer solution have the great advantage that they can be used without heating, but may, where appropriate, if the radiopharmacy is not from time to time equipped with a complexation instrument without a heating device, be used in an instrument with a heating device.
- Various automic complexationinstruments may be used, for instance equiped with known either cationic or anionic resins.
- the invention relates to an instrument (complexation system), which is preferably automatic, without a heating device, comprising at least one compartment for mixing a solution of radionuclide provided by a radionuclide generator, more especially a Ga68 generator, a solution of noncomplexed vectorized chelate and a buffer solution, said buffer being chosen from lactate, tartrate, maleate, succinate, malate, ascorbate, carbonate and phosphate and mixtures thereof.
- a radionuclide generator more especially a Ga68 generator
- a solution of noncomplexed vectorized chelate and a buffer solution
- the buffer being chosen from lactate, tartrate, maleate, succinate, malate, ascorbate, carbonate and phosphate and mixtures thereof.
- Any suitable device is prepared accordingly.
- the Ga68 provided is a sterile solution separated into single doses by the automated machine by means of a distribution device of the automated machine, or before the automated machine, with the use of single-dose containers introduced into the automated
- the automated machine comprises, for example, a mixing compartment capable of preparing several doses of injectable radiolabeled product for one or more patients.
- the automated machine may also comprise several mixing subcompartments, each compartment being able to mix a dose of Ga68 radionuclide in particular and a dose of vectorized product.
- the automated machine may be automatic.
- the automated machine which where appropriate is programmable, may also prepare several different injectable products, with identical or different biovectors, and different doses and concentrations, where appropriate as a function of the type of product to be produced and of the method of injection (manual or automatic injection).
- the various products, methods and instruments of the application may in addition be used for any appropriate imaging modalities, in particular PET imaging, multimodal imaging and, where appropriate, product multi- injections, in particular PET/MRI, PET/scan, PET/scan/MRI and optical imaging, with the analytical and image- processing methods.
- the invention thus relates to any medical imaging plant comprising a complexation instrument as described in the application, in combination with MRI and/or XR-scan and/or optical equipment. More as a whole, any equipment of the prior art (summarized in particular in WO2007/042504) suitable for the complexation compounds and conditions of the invention may be used.
- the detailed examples which follow demonstrate the effectiveness of the applicant's buffers (example 1)
- NOTA and PCTA chelates, and folate and peptides biovectors are emphasized that the one skilled in the art can thus prepare similar compounds with many other biovectors, many other linkers, many other chelates.
- the buffers are prepared at pH4. They are obtained by mixing the weak acid at 0.1M and the weak base at 0. IM.
- Citric A large amount of ligand ; a small amount of complex
- Step 5
- Step 6
- Step 7
- Step 8
- Example 5 chelates vectorized with a peptide
- PCTA chelate (compound of example 6 step 3 of WO 2007/042504 page 52 (corresponding formula not complexed by gallium), is coupled to peptides as shown in example 7 of WO 2007/042504 pages 52-53 2) for NOTA chelates :
- NOTA chelate (compound of example 4 of WO 2007/042504 page 49, not complexed by gallium), is coupled to peptides as shown in example 5 of WO 2007/042504 page 50 ;
- the illustrative compounds of WO 2007/042504 page 50 (corresponding formula not complexed by gallium) are peptides coupled to NOTA with different squarate linkers ; being precised that many other linkers such as (CH2)n, PEG are prepared similarly.
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Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201080010448.1A CN102341127B (en) | 2009-02-13 | 2010-02-11 | Use of buffers for radionuclide complexation |
JP2011549557A JP2012517974A (en) | 2009-02-13 | 2010-02-11 | Use of buffers for radionuclide complexation. |
CA2752181A CA2752181C (en) | 2009-02-13 | 2010-02-11 | Use of buffers for radionuclide complexation |
US13/201,115 US20120009124A1 (en) | 2009-02-13 | 2010-02-11 | Use of buffers for radionuclide complexation |
EP10703282.3A EP2396040B1 (en) | 2009-02-13 | 2010-02-11 | Use of buffers for radionuclide complexation |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0950944A FR2942227B1 (en) | 2009-02-13 | 2009-02-13 | USE OF BUFFERS FOR RADIONUCLEID COMPLEXATION |
FR0950944 | 2009-02-13 | ||
US15465009P | 2009-02-23 | 2009-02-23 | |
US61/154,650 | 2009-02-23 |
Publications (1)
Publication Number | Publication Date |
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WO2010092114A1 true WO2010092114A1 (en) | 2010-08-19 |
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ID=40873380
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2010/051709 WO2010092114A1 (en) | 2009-02-13 | 2010-02-11 | Use of buffers for radionuclide complexation |
Country Status (8)
Country | Link |
---|---|
US (1) | US20120009124A1 (en) |
EP (1) | EP2396040B1 (en) |
JP (1) | JP2012517974A (en) |
KR (1) | KR20110115606A (en) |
CN (1) | CN102341127B (en) |
CA (1) | CA2752181C (en) |
FR (1) | FR2942227B1 (en) |
WO (1) | WO2010092114A1 (en) |
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Citations (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1994000489A2 (en) | 1992-06-23 | 1994-01-06 | Diatech, Inc. | Radioactively-labeled somatostantin-derived peptides for imaging and therapeutic uses |
WO1994005269A1 (en) | 1992-09-08 | 1994-03-17 | Centocor, Inc. | Peptide inhibitors of selectin binding |
EP0661279A1 (en) | 1993-12-30 | 1995-07-05 | Guerbet S.A. | Polyaminated ligands, metal complexes, process for their preparation and diagnostic and therapeutic applications |
US5707605A (en) | 1995-06-02 | 1998-01-13 | Research Corporation Technologies | Magnetic resonance imaging agents for the detection of physiological agents |
WO1999040947A2 (en) | 1998-02-11 | 1999-08-19 | Resolution Pharmaceuticals Inc. | Angiogenesis targeting molecules |
WO1999054317A1 (en) | 1998-04-23 | 1999-10-28 | Cortech Inc. | Cysteine protease inhibitors |
WO2001009188A1 (en) | 1999-07-29 | 2001-02-08 | Dyax Corp. | Binding moieties for fibrin |
WO2001010450A1 (en) | 1999-08-10 | 2001-02-15 | Imarx Therapeutics, Inc. | Targeted thrombolytic agents |
US6261535B1 (en) | 1992-03-05 | 2001-07-17 | The University Of Texas System Board Of Regents | Diagnostic methods for targeting the vasculature of solid tumors |
US6264914B1 (en) | 1996-10-28 | 2001-07-24 | Nycomed Imaging As | Contrast agents |
EP1121377A1 (en) | 1998-10-13 | 2001-08-08 | Du Pont Pharmaceuticals Company | Chelator incorporated arg-gly-asp (rgd) mimetic synthetic disintegrins as imaging agents |
WO2001060416A2 (en) | 2000-02-15 | 2001-08-23 | Bristol-Myers Squibb Pharma Company | Matrix metalloproteinase inhibitors as targeting components in diagnostic agents |
WO2001077145A2 (en) | 2000-04-12 | 2001-10-18 | Amersham Health As | Integrin binding peptide derivatives |
WO2001077102A1 (en) | 2000-04-07 | 2001-10-18 | Bristol-Myers Squibb Pharma Company | Macrocyclic chelants for metallopharmaceuticals |
WO2001097861A2 (en) | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
WO2001097850A2 (en) | 2000-06-23 | 2001-12-27 | Schering Aktiengesellschaft | Combinations and compositions which interfere with vegf/vegf and angiopoietin/tie receptor function and their use (ii) |
WO2001098294A2 (en) | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals for use in combination therapy |
WO2002026776A2 (en) | 2000-09-26 | 2002-04-04 | Amersham Health As | Peptide-based compounds |
WO2002028441A2 (en) | 2000-10-04 | 2002-04-11 | California Institute Of Technology | Magnetic resonance imaging agents for in vivo labeling and detection of amyloid deposits |
US6372194B1 (en) | 1997-03-18 | 2002-04-16 | Toshihiro Akaike | MRI contrast media recognizing minor environmental changes |
WO2002032292A2 (en) | 2000-10-18 | 2002-04-25 | The Board Of Trustess Of The Leland Stanford Junior University | Methods for development and use of diagnostic and therapeutic agents |
WO2002038546A1 (en) | 2000-11-08 | 2002-05-16 | K.U. Leuven Research & Development | Substituted bis-indole derivatives useful as contrast agents, pharmaceutical compositions containing them and intermediates for producing them |
US6391280B1 (en) | 1997-01-10 | 2002-05-21 | Epicyte Pharmaceutical, Inc. | J chain polypeptide targeting molecule linked to an imaging agent |
WO2002040060A2 (en) | 2000-10-31 | 2002-05-23 | Bracco International Bv | Conjugates of an antioxidants with metal chelating ligands |
WO2002044156A2 (en) | 2000-11-29 | 2002-06-06 | Glaxo Group Limited | Benzimidazole derivatives useful as tie-2 and/or vegfr-2 inhibitors |
US6410695B1 (en) | 1995-02-21 | 2002-06-25 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Individual medicament dosing conjugate |
WO2002054088A2 (en) | 2001-01-05 | 2002-07-11 | Duke University | Contrast enhancement agent for magnetic resonance imaging |
WO2002056670A2 (en) | 2001-01-05 | 2002-07-25 | The General Hospital Corporation | Activatable imaging probes |
WO2002059110A1 (en) | 2000-12-21 | 2002-08-01 | Glaxo Group Limited | Pyrimidineamines as angiogenesis modulators |
US20020106325A1 (en) | 2000-11-27 | 2002-08-08 | Carpenter, Alan P. | Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent |
WO2002062810A2 (en) | 2000-11-29 | 2002-08-15 | Bracco International B.V. | Linkable sialyl lewis x analogs |
US6440956B1 (en) | 1999-06-09 | 2002-08-27 | Guerbet | Bicyclic polyaminoacid metal complexes, their process of preparation and their application in medical imaging |
WO2002066512A1 (en) | 2001-02-16 | 2002-08-29 | E.I. Dupont De Nemours And Company | Angiogenesis-inhibitory tripeptides, compositions and their methods of use |
US20020128553A1 (en) | 2001-03-12 | 2002-09-12 | Hadasit Medical Research Services And Development Ltd. | Radiolabeled irreversible inhibitors of epidermal growth factor receptor tyrosine kinase and their use in radioimaging and radiotherapy |
WO2002081497A2 (en) | 2001-04-04 | 2002-10-17 | University Of Rochester | αξβ3 INTEGRIN-BINDING POLYPEPTIDE MONOBODIES AND THEIR USE |
WO2002085908A1 (en) | 2001-04-24 | 2002-10-31 | Purdue Research Foundation | Folate mimetics and folate-receptor binding conjugates thereof |
WO2002085903A2 (en) | 2001-04-23 | 2002-10-31 | The Trustees Of The University Of Pennsylvania | Amyloid plaque aggregation inhibitors and diagnostic imaging agents |
WO2002094873A2 (en) | 2001-05-22 | 2002-11-28 | Bracco Imaging S.P.A. | Preparation of cholecystokinin agonists and antagonists, and their therapeutic and diagnostic use |
US6489333B2 (en) | 1998-04-01 | 2002-12-03 | Bristol - Meyers Squibb Pharma Company | Integrin antagonists |
US6491893B1 (en) | 1999-01-19 | 2002-12-10 | Biostream, Inc. | Compounds for targeting and imaging infection and inflammation |
WO2003006059A1 (en) | 2001-07-13 | 2003-01-23 | Imclone Systems Incorporated | Vegfr-1 antibodies to treat breast cancer |
US6511648B2 (en) | 1998-12-18 | 2003-01-28 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
WO2003011115A2 (en) | 2001-07-30 | 2003-02-13 | Epix Medical, Inc. | Peptide-based multimeric targeted contrast agents |
WO2003014145A2 (en) | 2001-08-10 | 2003-02-20 | Novartis Ag | Peptides that bind to atherosclerotic lesions |
US6524554B1 (en) | 1998-04-03 | 2003-02-25 | Bristol-Myers Squibb Pharma Company | Radiopharmaceuticals for imaging infection and inflammation and for imaging and treatment of cancer |
WO2003020701A2 (en) | 2001-09-04 | 2003-03-13 | Texas Tech University | Multi-use multimodal imaging chelates |
US6534038B2 (en) | 2000-04-07 | 2003-03-18 | Bristol-Myers Squibb Pharma Company | Ternary ligand complexes useful as radiopharmaceuticals |
US6537520B1 (en) | 1998-03-31 | 2003-03-25 | Bristol-Myers Squibb Pharma Company | Pharmaceuticals for the imaging of angiogenic disorders |
WO2003062198A1 (en) | 2002-01-24 | 2003-07-31 | Barnes Jewish Hospital | Integrin targeted imaging agents |
WO2004089425A1 (en) | 2003-04-11 | 2004-10-21 | Ge Healthcare Limited | Microwave method for preparing radiolabelled gallium complexes |
WO2004112839A2 (en) | 2003-06-25 | 2004-12-29 | Guerbet | Specific high-relaxivity conjugate compounds for magnetic resonance imaging |
WO2005009393A2 (en) | 2003-07-24 | 2005-02-03 | Bracco Imaging S.P.A. | Stable radiopharmaceutical compositions and methods for preparation |
WO2006032704A2 (en) | 2004-09-23 | 2006-03-30 | Guerbet | Diagnostic compounds for targeting a chemokine receptor |
WO2006095234A2 (en) | 2005-03-03 | 2006-09-14 | Bracco Imaging S.P.A. | Integrin targeted synthetic ligands for diagnostic and therapeutic applications |
WO2007042504A2 (en) | 2005-10-07 | 2007-04-19 | Guerbet | Compounds comprising a biological target recognizing part, coupled to a signal part capable of complexing gallium |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5395946A (en) * | 1988-02-09 | 1995-03-07 | Goedemans; Wilhelmus T. | Bifunctional chelating agents |
US5476644A (en) * | 1994-04-13 | 1995-12-19 | Sterling Winthrop Inc. | Cyclic triamine chelating agents |
BR0207315A (en) * | 2001-02-26 | 2004-02-10 | Bristol Myers Squibb Pharma Co | Ascorbic acid analogues for metalloradiopharmaceuticals |
AR044852A1 (en) * | 2003-06-24 | 2005-10-05 | Novartis Ag | A PHARMACEUTICAL COMPOSITION FOR PARENTERAL ADMINISTRATION THAT INCLUDES A SOMATOSTATINE ANALOG |
GB0314695D0 (en) * | 2003-06-24 | 2003-07-30 | Novartis Ag | Organic compounds |
US20100143249A1 (en) * | 2007-04-11 | 2010-06-10 | Merck Eprova Ag | Folate-conjugates and corresponding metal-chelate complexes for use in diagnostic imaging and radiotherapy |
-
2009
- 2009-02-13 FR FR0950944A patent/FR2942227B1/en not_active Expired - Fee Related
-
2010
- 2010-02-11 US US13/201,115 patent/US20120009124A1/en not_active Abandoned
- 2010-02-11 WO PCT/EP2010/051709 patent/WO2010092114A1/en active Application Filing
- 2010-02-11 EP EP10703282.3A patent/EP2396040B1/en not_active Not-in-force
- 2010-02-11 JP JP2011549557A patent/JP2012517974A/en active Pending
- 2010-02-11 CA CA2752181A patent/CA2752181C/en not_active Expired - Fee Related
- 2010-02-11 KR KR1020117021102A patent/KR20110115606A/en not_active Application Discontinuation
- 2010-02-11 CN CN201080010448.1A patent/CN102341127B/en not_active Expired - Fee Related
Patent Citations (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6261535B1 (en) | 1992-03-05 | 2001-07-17 | The University Of Texas System Board Of Regents | Diagnostic methods for targeting the vasculature of solid tumors |
WO1994000489A2 (en) | 1992-06-23 | 1994-01-06 | Diatech, Inc. | Radioactively-labeled somatostantin-derived peptides for imaging and therapeutic uses |
WO1994005269A1 (en) | 1992-09-08 | 1994-03-17 | Centocor, Inc. | Peptide inhibitors of selectin binding |
EP0661279A1 (en) | 1993-12-30 | 1995-07-05 | Guerbet S.A. | Polyaminated ligands, metal complexes, process for their preparation and diagnostic and therapeutic applications |
US5919432A (en) | 1993-12-30 | 1999-07-06 | Guerbet S.A. | Polyaminated ligands and metal complexes thereof |
US6410695B1 (en) | 1995-02-21 | 2002-06-25 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Individual medicament dosing conjugate |
US5707605A (en) | 1995-06-02 | 1998-01-13 | Research Corporation Technologies | Magnetic resonance imaging agents for the detection of physiological agents |
US6264914B1 (en) | 1996-10-28 | 2001-07-24 | Nycomed Imaging As | Contrast agents |
US6391280B1 (en) | 1997-01-10 | 2002-05-21 | Epicyte Pharmaceutical, Inc. | J chain polypeptide targeting molecule linked to an imaging agent |
US6372194B1 (en) | 1997-03-18 | 2002-04-16 | Toshihiro Akaike | MRI contrast media recognizing minor environmental changes |
WO1999040947A2 (en) | 1998-02-11 | 1999-08-19 | Resolution Pharmaceuticals Inc. | Angiogenesis targeting molecules |
US6537520B1 (en) | 1998-03-31 | 2003-03-25 | Bristol-Myers Squibb Pharma Company | Pharmaceuticals for the imaging of angiogenic disorders |
US6489333B2 (en) | 1998-04-01 | 2002-12-03 | Bristol - Meyers Squibb Pharma Company | Integrin antagonists |
US6524554B1 (en) | 1998-04-03 | 2003-02-25 | Bristol-Myers Squibb Pharma Company | Radiopharmaceuticals for imaging infection and inflammation and for imaging and treatment of cancer |
WO1999054317A1 (en) | 1998-04-23 | 1999-10-28 | Cortech Inc. | Cysteine protease inhibitors |
EP1121377A1 (en) | 1998-10-13 | 2001-08-08 | Du Pont Pharmaceuticals Company | Chelator incorporated arg-gly-asp (rgd) mimetic synthetic disintegrins as imaging agents |
US6511648B2 (en) | 1998-12-18 | 2003-01-28 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
US6491893B1 (en) | 1999-01-19 | 2002-12-10 | Biostream, Inc. | Compounds for targeting and imaging infection and inflammation |
US6440956B1 (en) | 1999-06-09 | 2002-08-27 | Guerbet | Bicyclic polyaminoacid metal complexes, their process of preparation and their application in medical imaging |
WO2001009188A1 (en) | 1999-07-29 | 2001-02-08 | Dyax Corp. | Binding moieties for fibrin |
WO2001010450A1 (en) | 1999-08-10 | 2001-02-15 | Imarx Therapeutics, Inc. | Targeted thrombolytic agents |
WO2001060416A2 (en) | 2000-02-15 | 2001-08-23 | Bristol-Myers Squibb Pharma Company | Matrix metalloproteinase inhibitors as targeting components in diagnostic agents |
WO2001077102A1 (en) | 2000-04-07 | 2001-10-18 | Bristol-Myers Squibb Pharma Company | Macrocyclic chelants for metallopharmaceuticals |
US6534038B2 (en) | 2000-04-07 | 2003-03-18 | Bristol-Myers Squibb Pharma Company | Ternary ligand complexes useful as radiopharmaceuticals |
WO2001077145A2 (en) | 2000-04-12 | 2001-10-18 | Amersham Health As | Integrin binding peptide derivatives |
WO2001098294A2 (en) | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals for use in combination therapy |
WO2001097861A2 (en) | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | Vitronectin receptor antagonist pharmaceuticals |
WO2001097850A2 (en) | 2000-06-23 | 2001-12-27 | Schering Aktiengesellschaft | Combinations and compositions which interfere with vegf/vegf and angiopoietin/tie receptor function and their use (ii) |
WO2002026776A2 (en) | 2000-09-26 | 2002-04-04 | Amersham Health As | Peptide-based compounds |
WO2002028441A2 (en) | 2000-10-04 | 2002-04-11 | California Institute Of Technology | Magnetic resonance imaging agents for in vivo labeling and detection of amyloid deposits |
WO2002032292A2 (en) | 2000-10-18 | 2002-04-25 | The Board Of Trustess Of The Leland Stanford Junior University | Methods for development and use of diagnostic and therapeutic agents |
WO2002040060A2 (en) | 2000-10-31 | 2002-05-23 | Bracco International Bv | Conjugates of an antioxidants with metal chelating ligands |
WO2002038546A1 (en) | 2000-11-08 | 2002-05-16 | K.U. Leuven Research & Development | Substituted bis-indole derivatives useful as contrast agents, pharmaceutical compositions containing them and intermediates for producing them |
US20020106325A1 (en) | 2000-11-27 | 2002-08-08 | Carpenter, Alan P. | Simultaneous imaging of cardiac perfusion and a vitronectin receptor targeted imaging agent |
WO2002062810A2 (en) | 2000-11-29 | 2002-08-15 | Bracco International B.V. | Linkable sialyl lewis x analogs |
WO2002044156A2 (en) | 2000-11-29 | 2002-06-06 | Glaxo Group Limited | Benzimidazole derivatives useful as tie-2 and/or vegfr-2 inhibitors |
WO2002059110A1 (en) | 2000-12-21 | 2002-08-01 | Glaxo Group Limited | Pyrimidineamines as angiogenesis modulators |
WO2002054088A2 (en) | 2001-01-05 | 2002-07-11 | Duke University | Contrast enhancement agent for magnetic resonance imaging |
WO2002056670A2 (en) | 2001-01-05 | 2002-07-25 | The General Hospital Corporation | Activatable imaging probes |
WO2002066512A1 (en) | 2001-02-16 | 2002-08-29 | E.I. Dupont De Nemours And Company | Angiogenesis-inhibitory tripeptides, compositions and their methods of use |
US20020128553A1 (en) | 2001-03-12 | 2002-09-12 | Hadasit Medical Research Services And Development Ltd. | Radiolabeled irreversible inhibitors of epidermal growth factor receptor tyrosine kinase and their use in radioimaging and radiotherapy |
WO2002081497A2 (en) | 2001-04-04 | 2002-10-17 | University Of Rochester | αξβ3 INTEGRIN-BINDING POLYPEPTIDE MONOBODIES AND THEIR USE |
WO2002085903A2 (en) | 2001-04-23 | 2002-10-31 | The Trustees Of The University Of Pennsylvania | Amyloid plaque aggregation inhibitors and diagnostic imaging agents |
WO2002085908A1 (en) | 2001-04-24 | 2002-10-31 | Purdue Research Foundation | Folate mimetics and folate-receptor binding conjugates thereof |
WO2002094873A2 (en) | 2001-05-22 | 2002-11-28 | Bracco Imaging S.P.A. | Preparation of cholecystokinin agonists and antagonists, and their therapeutic and diagnostic use |
WO2003006059A1 (en) | 2001-07-13 | 2003-01-23 | Imclone Systems Incorporated | Vegfr-1 antibodies to treat breast cancer |
WO2003011115A2 (en) | 2001-07-30 | 2003-02-13 | Epix Medical, Inc. | Peptide-based multimeric targeted contrast agents |
WO2003014145A2 (en) | 2001-08-10 | 2003-02-20 | Novartis Ag | Peptides that bind to atherosclerotic lesions |
WO2003020701A2 (en) | 2001-09-04 | 2003-03-13 | Texas Tech University | Multi-use multimodal imaging chelates |
WO2003062198A1 (en) | 2002-01-24 | 2003-07-31 | Barnes Jewish Hospital | Integrin targeted imaging agents |
WO2004089425A1 (en) | 2003-04-11 | 2004-10-21 | Ge Healthcare Limited | Microwave method for preparing radiolabelled gallium complexes |
WO2004112839A2 (en) | 2003-06-25 | 2004-12-29 | Guerbet | Specific high-relaxivity conjugate compounds for magnetic resonance imaging |
WO2005009393A2 (en) | 2003-07-24 | 2005-02-03 | Bracco Imaging S.P.A. | Stable radiopharmaceutical compositions and methods for preparation |
WO2006032704A2 (en) | 2004-09-23 | 2006-03-30 | Guerbet | Diagnostic compounds for targeting a chemokine receptor |
WO2006095234A2 (en) | 2005-03-03 | 2006-09-14 | Bracco Imaging S.P.A. | Integrin targeted synthetic ligands for diagnostic and therapeutic applications |
WO2007042504A2 (en) | 2005-10-07 | 2007-04-19 | Guerbet | Compounds comprising a biological target recognizing part, coupled to a signal part capable of complexing gallium |
Non-Patent Citations (8)
Title |
---|
"Bioorganic & Medicinal Chemistry Letters", vol. 10, 2000, pages: 2133 - 2135 |
BIOORGANIC & MEDICINAL CHEMISTRY, vol. 11, 2003, pages 1319 - 1341 |
BIOVECTORS SUMMARIZED IN TOPICS IN CURRENT CHEMISTRY, vol. 222, pages 260 - 274 |
MULLER ET AL., EUR. J. ORG. CHEM, 2002, pages 3966 - 3973 |
PHARMACOLOGICAL REVIEWS, vol. 52, no. 2, pages 179 |
VELIKYAN ET AL., BIOCONJUGATE CHEM, vol. 19, 2008, pages 569 - 573 |
VELIKYAN I ET AL: "Convenient preparation of <68>Ga-based PET-radiopharmaceuticals at room temperature", BIOCONJUGATE CHEMISTRY 200802 US, vol. 19, no. 2, February 2008 (2008-02-01), pages 569 - 573, XP002546370, ISSN: 1043-1802 * |
W.KRAUSE: "Topics in Current Chemistry", vol. 222, SPRINGER |
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CN102341127B (en) | 2014-08-27 |
EP2396040A1 (en) | 2011-12-21 |
CA2752181C (en) | 2018-03-06 |
FR2942227A1 (en) | 2010-08-20 |
JP2012517974A (en) | 2012-08-09 |
KR20110115606A (en) | 2011-10-21 |
EP2396040B1 (en) | 2017-04-05 |
FR2942227B1 (en) | 2011-04-15 |
CA2752181A1 (en) | 2010-08-19 |
CN102341127A (en) | 2012-02-01 |
US20120009124A1 (en) | 2012-01-12 |
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