[Triumf-seminars] TRIUMF Colloquium today at 14:00

[TRIUMF Seminars]

Date/Time: Thu 2014-09-04 at 14:00

Location:  Auditorium          

Speaker:   Zhengxin Cai (U Pittsburgh)

Title:     64Cu-Labeled Somatostatin Analogues, from Illuminating the Target to Their Novel Applications

Abstract: Copper radionuclides offer versatile choices for applications in imaging, therapy, or theranostics. Copper-64, with a half-life of 12.7 h, and its unique decay profile (beta+: 18%; beta-: 38%; electron capture: 44%), is well suited for radiolabeling nanoparticles, antibodies, peptides, or small molecules for PET imaging and radiotherapy. This talk accounts our development of copper chelators, the bioconjugation strategies, the evaluations of the radiopharmaceuticals, and their applications in PET imaging of cancer and virus infection. It is complemented with relatively brief accounts of other projects, including PET imaging using 64Cu-labeled EGFR-targeted antibody cetuximab, 18F-labeled fatty acids, 18F-labeled p62 ligand, 11C-labeled CB2 ligand, and development of new solid phase radiolabeling strategies. 

Somatostatin receptor type 2 (sstr2) is a G-protein coupled receptor that is overexpressed in many neuroendocrine tumors. We were the first to redefine the 3D atomic structure of sstr2, using opioid receptor as the analogous model. After validation of this model by docking with known sstr2 ligands, we used it to test our newly synthesized somatostatin analogues in silico. These new somatostatin analogues were synthesized through bioorthogonal click chemistry, such as strain-promoted azide alkyne coupling reaction, hydrazone or oxime formation reactions, and copper-catalyzed click chemistry, using newly developed cross-bridged copper chelators. Knowledge of structure-pharmacokinetic relationship was gained by PET imaging and biodistribution studies with mouse xenograft. Then, we used sstr2 as the gene reporter to image viral infection using mouse models, and compared it with two other gene reporters which applied bioluminescent imaging and magnetic resonance imaging.

Refreshments 15 minutes before the talk.

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