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Pitchumony T.S.,McMaster University | Banevicius L.,McMaster University | Janzen N.,McMaster University | Zubieta J.,Syracuse University | And 2 more authors.
Inorganic Chemistry | Year: 2013

A convenient method to prepare 99mTc analogues of a class of rhenium(I) luminophores was developed, creating isostructural pairs of nuclear and optical probes. A two-step procedure and a new one-pot procedure were used to produce a series of [2 + 1] complexes of the type [Tc(CO)3(bipy)L] + in greater than 80% yield. The plasma stability of the reported compounds was evaluated, where the basicity of the monodentate pyridine type ligand (L) has a significant impact with half-lives ranging from 2 to 20 h. The ability to generate the radioactive complexes makes it possible to quantitate cell uptake of Re luminophores, which was demonstrated in MCF-7 breast cancer cells using 99mTc analogues of two Re(I)-based mitochondrial targeting dyes. © 2013 American Chemical Society.

Genady A.R.,McMaster University | Genady A.R.,Tanta University | Janzen N.,McMaster University | Banevicius L.,McMaster University | And 4 more authors.
Journal of Medicinal Chemistry | Year: 2016

The feasibility of developing a single agent that can deliver radioactive iodine and also direct cellular immune function by engaging endogenous antibodies as an antibody-recruiting small molecule (ARM) was determined. A library of new prostate-specific membrane antigen (PSMA)-binding ligands that contained antibody-recruiting 2,4-dinitrophenyl (DNP) groups and iodine were synthesized and screened in vitro and in vivo. A lead compound (9b) showed high affinity for PSMA and the ability to bind anti-DNP antibodies. Biodistribution studies of the iodine-125 analogue showed 3% ID/g in LNCaP xenograft tumors at 1 h postinjection with tumor-to-blood and tumor-to-muscle ratios of 10:1 and 44:1, respectively. The radiolabeled analogue was bound and internalized by LNCaP cells, with both functions blocked using a known PSMA inhibitor. A second candidate showed high tumor uptake (>10% ID/g) but had minimal binding to anti-DNP antibodies. The compounds reported represent the first examples of small molecules developed specifically for combination immunotherapy and radiotherapy for prostate cancer. © 2016 American Chemical Society.

Center For Probe Development And Commercialization | Date: 2011-06-07

diagnostic and therapeutic radiopharmaceutical preparations. imaging probes for diagnostic and medical use and molecular probes for therapeutic use. manufacturing of imaging probes and therapeutic agents for others. Development and commercialization of radiopharmaceuticals; development and commercialization of imaging probes; consulting services in the field of imaging probe development and the development of radiopharmaceuticals; project management in the field of probe development and the development of radiopharmaceuticals; chemistry lab services for radiopharmaceuticals; biological lab services for radiopharmaceuticals; pre-clinical and clinical research and trials in the field of radiopharmaceuticals; microbiology lab services; biological testing in the field of radiopharmaceuticals; drug product formulation development services. Providing assistance with regulatory matters in the field of radiopharmaceuticals for regulatory compliance purposes.

Center For Probe Development And Commercialization | Date: 2011-09-01

The application describes a method of radiolabeling a molecule comprising reacting the molecule and a radionuclide labeling reagent in an emulsion, such as an oil-in-water emulsion.

Edem P.E.,McMaster University | Czorny S.,McMaster University | Valliant J.F.,McMaster University | Valliant J.F.,Center for Probe Development and Commercialization
Journal of Medicinal Chemistry | Year: 2014

Dipeptidyl (acyloxy)methyl ketones (AOMKs) were functionalized with different iodine-containing prosthetic groups to generate a library of candidate cathepsin B probes. Compound 23a, (S)-20-[(S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido]-1-(4-iodophenyl)-1,14,21-trioxo-5,8,11-trioxa-2,15-diazadocosan-22-yl 2,4,6-trimethylbenzoate, was identified as a potential lead through in vitro screening, having a Ki = 181 ± 9 nM and demonstrating the ability to effectively label active cathepsin B in vitro. Its less potent analogue 11a, (S)-3-[(S)-2-{[(benzyloxy)carbonyl]amino}-3-phenylpropanamido]-7-[6-(4-iodobenzamido)hexanamido]-2-oxoheptyl 2,4,6-trimethylbenzoate, was also tested as a comparison. Biodistribution studies of the iodine-125-labeled compounds in MDA-MB-231 mouse xenografts exhibited tumor uptake of 0.58% ± 0.06% injected dose per gram (ID/g) for [125I]11a and 1.12% ± 0.08% ID/g for [125I]23a at 30 min. The tumor-to-blood ratios reached 1.2 for [125I]23a and 1.6 for [125I]11a after 23 h. The more hydrophilic [125I]23a showed an improved clearance profile with a superior tumor-to-muscle ratio of 7.0 compared to 3.4 for [125I]11a at 23 h. Iodinated AOMK ligands are suitable in vitro probes for cathepsin B and hold promise as a platform to develop molecular imaging probes. © 2014 American Chemical Society.

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