The present disclosure relates to the synthesis of radionuclide complex solutions, in particular for their use in the commercial production of radioactive drug substances, for diagnostic and/or therapeutic purposes. In particular, the synthesis method comprises the following steps in the following order: a. providing a radionuclide precursor solution into a first vial, b. transferring the radionuclide precursor solution into a reactor, c. providing a reaction buffer solution into said first vial containing residual radionuclide precursor solution, d. transferring the buffer reaction solution and residual radionuclide precursor solution from said first vial into the reactor, e. transferring a peptide solution comprising the somatostatin receptor binding peptide linked to a chelating agent, into the reactor, f. reacting the somatostatin receptor binding peptide linked to a chelating agent with said radionuclide in the reactor to obtain the radionuclide complex, g. recovering said radionuclide complex.

A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radiolabeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa.sup.1-Xaa.sup.2a-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7a (I) or Xaa.sup.1-Xaa.sup.2b-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7b (II). Xaa.sup.1 is L-/D-Nle, L-/D-Nle, L-/D-Ala, L-/D-Leu, L-/D-Ile, D-Ile, L-/D-Cys, L-/D-Met, L-/D-Phe, L-/D-Trp, L-/D-Val, L-/D-Nal, L-/D-2-Nal, Gly, L-/D-α-aminobutyric acid, L-/D-norvaline, or L-/D-homonorleucine. Xaa.sup.2a and Xaa.sup.7b are L-/D-Cys, L-/D-Asp, L-/D-Glu, L-/D-2-Aad, L-/D-3-Aad, L-/D-Pra, L-/D-Hpg, or L-/D-Bpg. Xaa.sup.2b and Xaa.sup.7a are L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N.sub.3), L-/D-Orn(N.sub.3), L-/D-Dab(N.sub.3), L-/D-Dap(N.sub.3), L-/D-2-(5′-azidopentyl)alanine, or L-/D-2-(6′-azidohexyl)alanine. Xaa.sup.3 is L-/D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-N alanine. Xaa.sup.4 is L-/D-Phe, L-/D-2-Nal, L-/D-Phe(4-F), L-/D-Phe(4-Cl), L-/D-Phe(4-Br), L-/D-Phe(4-I), L-/D-Phe(4-NH.sub.2), or L-/D-Phe(4-NO.sub.2). Xaa.sup.5 is L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaa.sup.6 is L-/D-Trp, L-/D-Phe, L-/D-Trp(5-Br), L-/D-Trp(5-OCH.sub.3), L-/D-Trp(6-F), L-/D-Trp(5-OH) or L-/D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7b is alpha N-methylated. The linker comprises an albumin-binding group.

Compositions, methods, and uses of an alpha emitter are provided in which the alpha emitter is coupled to carrier protein via a cleavable coupling moiety. The coupling moiety is preferably cleavable in an acidic tumor microenvironment, and as such will enrich the alpha emitter upon cleavage within the tumor microenvironment.

This application relates to compounds of Formula I. R.sup.1a, R.sup.1b and R.sup.1c is —CO.sub.2H, —SO.sub.2H, —SO.sub.3H, —SO.sub.4H, —PO.sub.2H, —PO.sub.3H or —PO.sub.4H. R.sup.2 is a linker, e.g. butylene. R.sup.3 is a linkage, e.g. —O—, —S—, —S(O)—, S(O).sub.2—, —NHC(O)—, —C(O)NH—, or 1,2,3-triazole. R4 is —(CH.sub.2).sub.0-3CH(R.sup.7)(CH.sub.2).sub.0-3— wherein R.sup.7 is —(CH.sub.2).sub.5CH.sub.3 or certain aromatic fused-ring systems. R.sup.5 and R.sup.6 are hydrogen or methyl. Each Xaa.sup.1 (if present) is an amino acid. R.sup.X is a radiolabeling group, e.g.: a radiometal chelator optionally bound by a radiometal; an aryl substituted with a radioisotope; a prosthetic group containing a trifluoroborate; or a prosthetic group containing a silicon-fluorine-acceptor moiety. The compounds may be useful for imaging prostate-specific membrane antigen (PSMA)-expressing tissues or for treating PSMA-expressing diseases (e.g. cancer).

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A compound is provided comprising a melanocortin 1 receptor (MC1R) targeting peptide (MC1RTP), a radiolabeling group, and a linker joining the MC1RTP to the radio labeling group. The MC1RTP is linear or cyclized, and comprises a sequence of Formula I or Formula II: Xaa.sup.1-Xaa.sup.2a-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7a (I) or Xaa.sup.1-Xaa.sup.2b-Xaa.sup.3-Xaa.sup.4-Xaa.sup.5-Xaa.sup.6-Xaa.sup.7b (II). Xaa.sup.1 is L-/D-Nle, L-/D-Nle, L-/D-Ala, L-/D-Leu, L-/D-Ile, D-Ile, L-/D-Cys, L-/D-Met, L-/D-Phe, L-/D-Trp, L-/D-Val, L-/D-Nal, L-/D-2-Nal, Gly, L-/D-α-aminobutryic acid, L-/D-norvaline, or L-/D-homonorleucine. Xaa.sup.2a and Xaa.sup.7b are L-/D-Cys, L-/D-Asp, L-/D-Glu, L-/D-2-Aad, L-/D-3-Aad, L-/D-Pra, L-/D-Hpg, or L-/D-Bpg. Xaa.sup.2b and Xaa.sup.7a are L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N.sub.3), L-/D-Orn(N.sub.3), L-/D-Dab(N.sub.3), L-/D-Dap(N.sub.3), L-/D-2-(5′-azidopentyl)alanine, or L-/D-2-(6′-azidohexyl)alanine. Xaa.sup.3 is L-/D-His, Pro, beta-(1,2,3-triazol-4-yl)-L-alanine, beta-(1,2,3-triazol-4-yl)-D-alanine, 1,2,4-triazole-3-alanine, or 1,2,4-triazole-3-D-alanine. Xaa.sup.4 is L-/D-Phe, L-/D-2-Nal, L-/D-Phe(4-F), L-/D-Phe(4-Cl), L-/D-Phe(4-Br), L-/D-Phe(4-I), L-/D-Phe(4-NH2), or L-/D-Phe(4-NO2). Xaa.sup.5 is L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaa.sup.6 is L-/D-Trp, L-/D-Phe, L-/D-Trp(5-Br), L-/D-Trp(5-OCH3), L-/D-Trp(6-F), L-/D-Trp(5-OH) or L-/D-Trp(CHO). One or more amino acid residues of the MC1RTP is alpha N-methylated, wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7a is alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa.sup.3, Xaa.sup.5, Xaa.sup.6 and Xaa.sup.7b is alpha N-methylated. The linker comprises an albumin-binding group.

The invention provides a compound having the following structure:

D-DT-R,

wherein D is a dextran molecule or a charged dextran molecule having a molecular weight between about 50,000 and about 110,000 Daltons, DT is dodecane tetra-acetic acid (DOTA) or a conjugate base thereof, and R is a radioactive isotope. The invention also provides a method for treating body cavity cancer in a patient afflicted therewith, comprising administering an effective amount of a dextran—dodecane tetraacetic acid—radioactive isotope compound in a pharmaceutically effective vehicle.

The present disclosure relates to macrocyclic chelates including a macrocyclic chelating moiety of a metal complex thereof, a bifunctional linker, and a therapeutic or targeting moiety. Also disclosed are methods for preparation of the same, and use thereof.

The present disclosure provides for imaging agents and methods of making and using the same. The imaging agent comprises a luminol component comprising a luminol moiety or functional analogue thereof; a chelator; a linker group bonding or complexing the luminol component to the chelator; and a radiolabel component bound to the chelator. The imaging agent described herein is capable of monitoring, targeting, or imaging oxidative stress, reactive oxygen species (ROS), superoxide generation, or hydrogen peroxide generation, mediating pathophysiology of different disease states.

The invention relates to a marking precursor incorporating a chelator or fluorination group for radiolabelling with 44Sc, 47Sc, 55Co, 62Cu, 64Cu, 67Cu, 66Ga, 67Ga, 68Ga, 89Zr, 86Y, 90Y, 90Nb, 99mTc, 111ln, 135Sm, 140Pr, 159Gd, 149Tb, 160Tb, 161Tb, 165Er, 166Dy, 166Ho, 175Yb, 177Lu, 186Re, 188Re, 213Bi and 225Ac or with 18F, 131I or 211At, and one or two biological targeting vectors which are coupled to the chelator or fluorinating group via one or more squaric acid groups.

The present disclosure discloses methods and compositions for administering Cerenkov radiation-induced therapy (CRIT).