The University of British Columbia

Provincial Health Services Authority

British Columbia Cancer Agency Branch

Triumf

Triumf, a Joint Venture

François Bénard

Kuo-Shyan Lin

Zhengxing Zhang

David Perrin

Chengcheng Zhang

Kuo-shyan Lin

Paul Schaffer

Stefan K Zeisler

Zhibo Liu

Hsiou-Ting Kuo

Hsiou-ting Kuo

Jinhe Pan

Kenneth R Buckley

Thomas J Ruth

Kenneth Robert Buckley

Helen Merkens

Thomas J Morley

Mihajlo Todorovic

Victoire Hanemaayer

Felix Mesak

Sungjoon Huh

Milan Vuckovic

Mathieu Lepage

Rajaguru Kandasamy

John Valliant

Michael S Kovacs

Julius Alexander Klug

Cornelia Manuela Hoehr

Aron Roxin

Maurice G Dodd

Ivica Bratanovic

Maral Pourghiasian

Lei Wang

Cornelia Manuela

Cornelia Hoehr Manuela

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

A compound or molecular complex. The compound or molecular complex comprises: a metal chelator configured for chelation with a radioactive isotope or a non-radioactive isotope; and a trifluoroborate (BF)-containing moiety configured forF/F exchange or a precursor thereof; and optionally a cell-targeting domain.

Dual mode 18F-labelled theranostic compounds and uses thereof

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

The invention described herein is based in part on the discovery of a protein/peptide crosslink, which introduces fluorescent properties, and which has been applied to synthesize analogues of melanocortin and amanitin as choice peptides to be explored in the context of isoindole peptides. Without limitation, it is expected that those trained in the art of peptide synthesis and stapling would appreciate the consequences of this invention such that other peptides of varied length can be similarly constrained by isoindole staples as featured herein.

Cyclic peptide analogs of melanocortin and amanitin and methods of making such

A system for producing technetium-99m from molybdate-100. The system comprises: a target capsule apparatus for housing a Mo-100-coated target plate; a target capsule pickup apparatus for engaging, and delivering the target cell apparatus into a target station apparatus; target station apparatus for receiving and mounting therein the target capsule apparatus. The target station apparatus is engaged with a cyclotron for irradiating the Mo-100-coated target plate with protons. The irradiated target capsule apparatus is transferred to a receiving cell apparatus comprising a dissolution/purification module for receiving therein a proton-irradiated Mo-100-coated target plate. A conveyance conduit infrastructure interconnects: (i) the target capsule pickup apparatus with the target station apparatus, (ii) the target station apparatus and the receiving cell apparatus; and (iii) the receiving cell apparatus and the dissolution/purification module.

Processes, systems, and apparatus for cyclotron production of technetium-99m

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.

This disclosure relates to novel compounds comprising a zwitterionic trifluoroborate prosthetic group which target prostate-specific membrane antigen (PSMA), e.g. in prostate cancer. The compounds have Formula I, wherein each R1 is an anionic group, L is a linker and R2B-F3 is &#x2014;N(R)CHBF, a pyridinium group substituted with BFor methyl BF, or an azole group substituted with methyl BF3. Methods and uses of imaging and treating PSMA-expressing cancers are also disclosed. 

18/19F-labelled compounds which target the prostate specific membrane antigen

Somatostatin derivative compounds of general formula (I) that may be readily labelled with the isotope fluorine-18 and that have affinity and selectivity for cellular somatostatin receptors are provided. The labelled compounds are useful clinically as radioactive tracers in various in vivo imaging applications (for example, using positron emission tomography (PET) and related techniques) to detect somatostatin-expressing cells and tissues, including tumors, or as therapeutic agents.

Compositions and methods for imaging cancer

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.

Compositions targeting bradykinin receptor B1 for medical imaging of cancer and other disorders

Systems and methods for separation or isolation of technetium radioisotopes from aqueous solutions of radioactive or non-radioactive molybdate salts using a polyalkyl glycol-based cross-linked polyether polymer. Some embodiments can be used for the effective purification of radioactive technetium-99m produced from low specific activityMo.

Process and apparatus for separation of technetium-99M from molybdate

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Vancouver, Canada

François Bénard