Provincial Health Services Authority

The University of British Columbia

British Columbia Cancer Agency Branch

Zhengxing Zhang

François Bénard

Kuo-Shyan Lin

Chengcheng Zhang

Hsiou-Ting Kuo

David Perrin

Kuo-shyan Lin

Helen Merkens

Jinhe Pan

Lei Wang

Ivica Bratanovic

Felix Mesak

This application relates to compounds of Formula I. R, Rand Ris —COH, —SOH, —SOH, —SOH, —POH, —POH or —POH. Ris a linker, e.g. butylene. Ris a linkage, e.g. —O—, —S—, —S(O)—, S(O)—, —NHC(O)—, —C(O)NH—, or 1,2,3-triazole. R4 is —(CH)CH(R)(CH)— wherein Ris —(CH)CHor certain aromatic fused-ring systems. Rand Rare hydrogen or methyl. Each Xaa(if present) is an amino acid. Ris 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).

Radiolabelled compounds for diagnosis or treatment of prostate-specific membrane antigen- expressing cancer

There is provided peptidic compounds of Formula I, A or B(R-[linker]-R-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-ψ-Xaa-NH). Xaais D-Phe, Cpa, D-Cpa, Nal, D-Nal, 2-Nal, or D-2-Nal; Xaais Asn, Gln, Hse, Cit or His. Xaais Trp, Bta, Trp(Me), Trp(7-Me), Trp(6-Me), Trp(5-Me), Trp(4-Me), Trp(2-Me), Trp(7-F), Trp(6-F), Trp(5-F), Trp(4-F), Trp(5-OH), or αMe-Trp. Xaais Ala or Ser. Xaais Val, Cpg, or Tle. Xaais Gly, NMe-Gly, or D-Ala. Xaais His or NMe-His. Xaais Leu or Phe. Xaa-NHis a C-terminally amidated amino acid residue selected from Pro, 4-oxa-L-Pro, MeThz, or Thz. ψ represents a peptide bond or reduced peptide bond joining Xaato Xaa. Ris 1-5 radiolabeling groups. There is also provided the use of such compounds as imaging agents or therapeutic agents.

Radiolabeled compounds for in vivo imaging of gastrin-releasing peptide receptor (GRPR) and treatment of GRPR-related disorders

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-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa(I) or Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa(II). Xaais 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. Xaaand Xaaare 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. Xaaand Xaaare L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N), L-/D-Orn(N), L-/D-Dab(N), L-/D-Dap(N), L-/D-2-(5'-azidopentyl)alanine, or L-/D-2-(6′-azidohexyl)alanine. Xaais 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. Xaais 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). Xaais L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaais 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, Xaa, Xaaand Xaais alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa, Xaa, Xaaand Xaais alpha N-methylated. The linker comprises an albumin-binding group.

Radiolabeled melanocortin 1 receptor-specific alpha-melanocyte-stimulating hormone analogues for imaging or therapy

A compound comprising a prostate specific membrane antigen (PSMA)-targeting moiety of the following formula or of a salt or a solvate thereof. Ris O or S. Each of R, Rand Rmay be &#x2014;COH, &#x2014;SOH, &#x2014;SOH, &#x2014;POH, or &#x2014;POH, for example. Rmay be methylene or a derivative thereof, propylene or a derivative thereof, or a derivative of ethylene, optionally substituted. Ris 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. 

Radiolabeled compounds targeting the prostate-specific membrane antigen

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-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa(I) or Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa(II). Xaais 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-&#x3b1;-aminobutryic acid, L-/D-norvaline, or L-/D-homonorleucine. Xaaand Xaaare 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. Xaaand Xaaare L-/D-Cys, L-/D-Lys, L-/D-Orn, L-/D-Dab, L-/D-Dap, L-/D-Lys(N), L-/D-Orn(N), L-/D-Dab(N), L-/D-Dap(N), L-/D-2-(5'-azidopentyl)alanine, or L-/D-2-(6&#x2032;-azidohexyl)alanine. Xaais 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. Xaais 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). Xaais L-/D-Arg, L-/D-hArg), Leu, L-/D-Agb, or L-/D-Agp. Xaais 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, Xaa, Xaaand Xaais alpha N-methylated or wherein 1, 2, 3 or 4 of Xaa, Xaa, Xaaand Xaais alpha N-methylated. The linker comprises an albumin-binding group.

Bradykinin B1 receptor (B1R) targeting peptides and compounds are radiolabelled with radioisotopes that are suitable for imaging and/or radiotherapy. The radiolabelled peptides and compounds have utility in imaging tissues expressing or overexpressing B1R and/or treating diseases or conditions in which B1R is expressed or overexpressed, including cancer.

Growing community of inventors

Vancouver, Canada

Zhengxing Zhang