Fluorophore−Quencher Based Activatable Targeted Optical Probes for Detecting in Vivo Cancer Metastases

• DOI: 10.1021/mp800115t
• Publication Date: 2009-01-21T20:29:50Z
• Authors: Mikako Ogawa; Nobuyuki Kosaka; Michelle R. Longmire; Yasuteru Urano; Peter L. Choyke; Hisataka Kobayashi
• Keywords: Urothelial cancer

In vivo molecularly targeted fluorescence imaging of tumors has been proposed as a strategy for improving cancer detection and management. Activatable fluorophores, which increased their by 10-fold after binding tumor cells, result in much higher target to background ratios than conventional fluorophores. We developed an activatable optical probe based on fluorophore−quencher pair, bound targeting moiety. With this system, is quenched the interaction outside but activated within cells dissociation pair. selected TAMRA (fluorophore)−QSY7 (quencher) pair conjugated it either avidin (targeting d-galactose receptor) or trastuzumab (a monoclonal antibody against human epithelial growth factor receptor type2 (HER2/neu)) evaluated performance mouse models cancer. Two probes, TAMRA−QSY7 (Av-TM-Q7) (Traz-TM-Q7) were synthesized. Both demonstrated better similar self-quenching probes. vitro microscopic studies SHIN3 NIH/3T3/HER2+ that Av-TM-Q7 Traz-TM-Q7 produced high intracellular fluorescent signal. with mice enabled small tumors. This molecular probe, ligand, successfully detected due its activation ratio low Thus, these hold promise clinically "see treat" strategies