| 摘要 |
<p>Gallium-68 complex (I) is new. Gallium-68 complex (I) of formula Ch-L-B1 or Ch-L p-B1 q is new. Ch : chelate e.g. diethylene triamine pentaacetic acid (DTPA), 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), 1,4,7-triazacyclonane-1,4,7-triacetic acid (NOTA), 1,4,7,10-tetraazacyclododecane (DO3A), 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-triacetic acid (PCTA) or its derivatives of formula (II) e.g. (IIa)-(IIe); either MM1M2 : a pyridine core; or M : bond (when M1 and M2 are absent) or NR (when M1 and M2 are H or CH 3); R : CH 2CO 2, H or CHX-CO 2 (preferred); X : L-B1; L : linker e.g. P1-L1-P2 or (CH 2) n (preferred), (CH 2) nCO, (CH 2) nNHCO, NH 2-(CH 2) n-COOH, NH 2-CH 2-(CH 2-O-CH 2) n-COOH, (CH 2CH 2O) q(CH 2) r-CO-, (CH 2CH 2O) q(CH 2) r-NH-CO, (CH 2) n1CONH, (CH 2) n1, CONH-polyethylene glycol, (CH 2) n1NH, cyclobut-3-ene-1,2-dione derivative of formula (IIIa) or (IIIb), HOOCCH 2O(CH 2) 2O(CH 2) 2OCH 2COOH, HOOC-(CH 2) 2-CO 2-(CH 2) 2-OCO-(CH 2) 2-COOH, HOOC-CH(OH)-CH(OH)-COOH, HOOC-(CH 2) n2-COOH or NH 2-(CH 2) n2-NH 2; P1, P2 = O, S, NH, CO 2. NHCO, CONH, NHCONH, NHCSNH, SO 2NH or NHSO 2; L1 : alkyl, preferably 1-10C alkyl (where alkyl is interrupted by aryls, preferably phenyl, alkenyl e.g. 2-6C alkenyl, alkynyl e.g. 2-6C alkynyl, NH, O, CO, NH(CO), (CO)NH, O(CO) or (OC)O), alkoxyalkyl, preferably 1-10C alkoxyalkyl or polyalkoxyalkylene; n : 2-10; q : 1-10; r : 2-10; n1 : 1-5, preferably 4-5; n2 : 0-20; B1 : biovector of targeting of a biological target associated to a pathology, preferably enzymes like metalloproteases, cyclooxygenase or tyrosine kinase or vascular endothelial growth factor receptor, kinase insert domain-containing receptor, CXC receptor, luteinizing hormone-releasing hormone receptor, glycoprotein-IIb/IIIa receptor, bombesin/gastrin-releasing peptide receptor, gastrin receptor, vasoactive intestinal peptide receptor, cholecystokinin receptors, glucose transporter receptor or folate receptors; and p, q : 2-5. Independent claims are included for: (1) a composition comprising (I) and a linear chelate or non-complexed macrocyclic chelate at 0.01-100 mM, preferably 10-100 mM; (2) a composition comprising (I) and calcium; (3) a composition comprising (I) and radiolysis stabilizing agent; (4) a kit for administering a gallium (Ga68) complex marked product comprising (I) or the composition; (5) a diagnostic composition comprising a contrasting agent with gallium-68 detectable in positron emission tomography (PET) and another contrasting agent detectable in magnetic resonance imaging (MRI) and/or in computerized tomography (CT) scanner; (6) an imaging method comprising administering a contrast product with gallium-68 to detect a diagnostic zone by PET imaging and administering a contrast product with MRI or X-ray scanner to analyze specifically the diagnostic zones; (7) an imaging method comprising administering a contrast product with MRI or X-ray scanner to make primary analysis of the zones and administering a contrast product with radiomarking gallium-68 for secondary analysis; (8) a medical imaging installation of PET/CT, PET/MRI or PET/CT/MRI type comprising an imaging device to take measurements of PET/MRI or PET/CT or PET/CT/MRI imaging parameters with or without injection of the contrast product, an injection device of contrast product marked with gallium-68 connected to the patient, an injection device of a contrast product for X-ray or MRI imaging and optionally an analytical device and injector of the imaging product for X-ray or MRI according to the first measurement taken following the administration of radio marked product contrast in gallium 68; (9) a method of selecting compounds in PET image of gallium 68, comprising the selection of biovectors having an affinity at micro molar, preferably nanomolar concentration from a base of active pharmacological molecules, selection of chelate having an affinity constant log K of at least 10, preferably 20, 25, 30 or 35 with gallium-68 Ga 3+> in a linear or macrocyclic chelate bank, selection of chemical bonds (i.e. the linker) to couple the biovector with at least the chelate, synthesis of (I) by complexing B1-L-Ch with gallium-68 and PET imaging of (I); (10) a vectorized product usable in PET image with gallium-68 obtained by the process; and (11) the preparation of (I). [Image] [Image] [Image].</p> |
