The invention relates to methods of treating cancer with CTT1403 having specificity for prostate-specific membrane antigen (PSMA).

The present disclosure concerns luteinizing hormone receptor hormone (LHRH) compositions that can selectively bind to an LHRH receptor. Through the incorporation of radionuclides in the LHRH compositions, selective radiolabeling is made possible, allowing for identification of cells over-expressing the LHRH receptor, which is often a facet of an abnormally growing cell or a tumorigenic cell. The LHRH compositions can therefore provide for improved detection and monitoring of cancers associated with or caused by LHRH receptor over-expression.

Described herein are novel conjugates containing an inhibitor (e.g., a PSMA inhibitor, e.g., a gastrin-releasing peptide receptor inhibitor) and metal chelator that are covalently attached to a macromolecule (e.g., a nanoparticle, a polymer, a protein). Such conjugates exhibit distinct properties over the free, unbound inhibitor/chelator construct.

Described herein are novel conjugates containing an inhibitor (e.g., a PSMA inhibitor, e.g., a gastrin-releasing peptide receptor inhibitor) and metal chelator that are covalently attached to a macromolecule (e.g., a nanoparticle, a polymer, a protein). Such conjugates exhibit distinct properties over the free, unbound inhibitor/chelator construct.

Provided herein are radiopharmaceutical conjugate compositions and uses thereof. In one aspect, provided herein are conjugates that comprise a monocyclic peptide of 5 to 40 amino acid residues and a metal chelator configured to bind with a radionuclide. In some embodiments, the monocyclic peptide is cyclized by a non-disulfide bond. In some embodiments, the monocyclic peptide does not comprise any non-disulfide bond. The monocyclic peptide can be configured to bind with a structure on a cell. Further provided herein are methods of treating cancer by administering the described conjugates and compositions.

A compound comprising a prostate specific membrane antigen (PSMA)-targeting moiety of the following formula or of a salt or a solvate thereof. R.sup.0 is O or S. Each of R.sup.1a, R.sup.1b and R.sup.1c may be —CO.sub.2H, —SO.sub.2H, —SO.sub.3H, —PO.sub.2H, or —PO.sub.3H.sub.2, for example. R.sup.2 may be methylene or a derivative thereof, propylene or a derivative thereof, or a derivative of ethylene, optionally substituted. R.sup.3 is a linker. When the PSMA-targeting moiety is linked to a radiolabeling group, the compound may be used as an imaging agent or therapeutic agent for PSMA-expressing diseases/conditions.

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The invention generally relates to a smart drug delivery system for dual nuclear medical cytotoxic theranostics incorporating either (i) a first compound with the structure CT-L1-Chel-S1-TV or

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or (ii) a second compound with the structure Chel-S-TV and a third compound with the structure CT-L-TV. In the first, second and third compounds Chel is a radical of a chelating agent for complexing a radioisotope; CT is a radical of a cytotoxic compound; TV is a biological targeting vector; L1 and L are each linkers; S1, S2 and S are each spacers.

A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH.sub.2, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.

A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH.sub.2, wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.

There is provided a therapeutic conjugate comprising a fusion protein and a cytotoxic radionuclide, which cytotoxic radionuclide is bound to the fusion protein. The fusion protein comprises a certain HER2-binding region (HBR), a certain albumin-binding region (ABR) and a spacer region.