Pretargeting kit, method and agents used therein

A kit for targeted medical imaging and/or therapeutics, comprising at least one Pre-targeting Probe and at least one Effector Probe, which undergo [4+2] cycloaddition in vivo, wherein the Pre-targeting Probe comprises a Primary Targeting Moiety and a first Bio-orthogonal Reactive Group, and wherein the Effector Probe comprises an Effector Moiety and a second Bio-orthogonal Reactive Group, wherein either of the first or second Bio-orthogonal Reactive Groups is a dienophile, and the other of the first and second Bio-orthogonal Reactive Groups is a diene, wherein the dienophile is an 8-member ring dienophile comprising trans-cyclooctene satisfying formula (1):

• wherein the position of R is equatorial and the position of Ra is axial, wherein each of X, Y, R, and Ra independently denotes H, or, in at most six instances, a group selected from alkyl, aryl, O-aryl, O-alkyl, S-aryl, S-alkyl, S(O)-aryl, S(O)-alkyl, S(O)2-aryl, S(O)2-alkyl, Si-aryl, Si-alkyl, Si-O-alkyl, OCO-alkyl, OCO-aryl, SCO-alkyl, SCO-aryl, OCS-alkyl, OCS-aryl, SCS-alkyl, SCS-aryl, NR′R″ with R′ and R″ each independently being H or alkyl, aryl, C(═O)O-alkyl, C(═O)O-aryl, C(═S)O-alkyl, C(═S)O-aryl, C(═O)S-alkyl, C(═O)S-aryl, C(═S)S-alkyl, C(═S)S-aryl, C(═O)NR′R″ with R′ and R″ each independently being H, aryl or alkyl, NR′CO-alkyl with R′ being H, alkyl or aryl, NR′CO-aryl with R′ being H, alkyl or aryl, NR′C(═O)O-alkyl with R′ being H, alkyl, or aryl, NR′C(═O)O-aryl with R′ being H, alkyl or aryl, OCONR′-alkyl with R′ being H, alkyl or aryl, OCONR′-aryl with R′ being H, alkyl or aryl, NR′CONR″-alkyl with R′ and R″ each independently being H, alkyl or aryl, NR′CONR″-aryl with R′ and R″ each independently being H, alkyl or aryl, NR′CSNR″-alkyl with R′ and R″ each independently being H, alkyl or aryl, and NR′CSNR″-aryl with R′ and R″ each independently being H, alkyl or aryl, CR′NR″ with R′ and R″ each independently being H, alkyl or aryl;
• with one of R or Ra comprised in a Linker Moiety to the Pre-targeting Probe or the Effector Probe;
• wherein two R or Ra moieties together may form a ring;
• wherein at least one and maximally four of Ra is not hydrogen,
• wherein the Primary Targeting Moiety is selected from the group of antibodies;
• antibody fragments selected from Fab2, Fab, scFV and diabodies;
• polymers which are tumor targeting by virtue of the enhanced permeability and retention (EPR)-effect;
• proteins;
• peptides;
• carbohydrates;
• monosaccharides;
• polysaccharides;
• viruses;
• whole cells;
• phage;
• drugs;
• chemotherapeutic agents, receptor agonists and antagonists, cytokines, hormones, steroids, and;
• nucleic acids;
• wherein the Effector Moiety is a detectable label selected from the group consisting of MRI-imageable agents being a superparamagnetic particle or a paramagnetic ion selected from Gd, Fe, Mn, Cr, Co, Ni, Cu, Pr, Nd, Yb, Tb, Dy, Ho, Er, Sm, Eu, Ti, Pa, La, Sc, V, Mo, Ru, Ce, Dy, Tl;
• spin labels;
• optical labels;
• an ultrasound-responsive agent being a microbubble, the shell of which is selected from a phospholipid, a (biodegradable) polymer, and human serum albumin;
• X-ray-responsive agents selected from iodine, barium, barium sulfate, gastrografin, a vesicle filled with iodine compounds and/or barium sulfate, a liposome filled with iodine compounds and/or barium sulfate, and a polymer capsule filled with iodine compounds and/or barium sulfate;
• radionuclides selected from 3H, 11C, 13N, 15O, 18F, 51Cr, 52Fe, 52Mn, 55Co, 60Cu, 61Cu, 62Zn, 62Cu, 63Zn, 64Cu, 66Ga, 67Ga, 68Ga, 70As, 71As, 72As, 74As, 75Se, 75Br, 76Br, 77Br, 8OBr, 82Br, 82Rb, 86Y, 88Y, 89Sr, 89Zr, 97Ru, 99Tc, 110In, 111In, 113In, 114In, 117Sn, 120I, 122Xe, 123I, 124I, 125I, 166Ho, 167Tm, 169Yb, 193Pt, 195Pt, 201Tl, and 203Pb;
• FRET-type dyes;
• (bio)luminescent or fluorescent molecules or tags;
• biotin;
• small size organic PET and SPECT labels selected from 18F, 11C and 123I;
• and/or wherein the Effector Moiety is a therapeutic moiety, a drug or a radioactive isotope for radiation therapy selected from 24Na, 32P, 33P, 47Sc, 59Fe, 67Cu, 76As, 77As, 80Br, 82Br, 89Sr, 90Nb, 90Y, 103Ru, 105Rh, 109Pd, 111Ag, 121Sn, 127Te, 131I, 140La, 141Ce, 142Pr, 143Pr, 144Pr, 149Pm, 149Tb, 151Pm, 153Sm, 159Gd, 161Tb, 165Dy, 166Dy, 166Ho, 169Er, 172Tm, 175Yb, 177Lu, 186Re, 188Re, 198Au, 199Au, 211At, 211Bi, 212Bi, 212Pb, 213Bi, 214Bi, 223Ra, and 225Ac.