Carbon-11 labeled BLZ945 as PET tracer for Colony Stimulating Factor 1 Receptor imaging in the brain
WILEY. 2019: S487–S488
View details for Web of Science ID 000468965200407
Near-Infrared Fluorescent Rosol Dye Tailored toward Lymphatic Mapping Applications
2019; 91 (4): 3110–17
An optical molecular imaging contrast agent that is tailored toward lymphatic mapping techniques implementing near-infrared (NIR) fluorescence image-guided navigation in the planning and surgical treatment of cancers would significantly aid in enabling the real-time visualization of the potential metastatic tumor-draining lymph node(s) for their needed surgical biopsy and/or removal, thereby ensuring unmissed disease to prevent recurrence and improve patient survival rates. Here, the development of the first NIR fluorescent rosol dye (THQ-Rosol) tailored to overcome the limitations arising from the suboptimal properties of the generic molecular fluorescent dyes commonly used for such applications is described. In developing THQ-Rosol, we prepared a progressive series of torsionally restrictive N-substituted non-NIR fluorescent rosol dyes based on density functional theory (DFT) calculations, wherein we discerned high correlations amongst their calculated energetics, modeled N-C3' torsion angles, and evaluated properties. We leveraged these strong relationships to rationally design THQ-Rosol, wherein DFT calculations inspired an innovative approach and synthetic strategy to afford an uncharged xanthene core-based scaffold/molecular platform with an aptly elevated p Ka value alongside NIR fluorescence emission (ca.700-900 nm). THQ-Rosol exhibited 710 nm NIR fluorescence emission, a 160 nm Stokes shift, robust photostability, and an aptly elevated p Ka value (5.85) for affording pH-insensitivity and optimal contrast upon designed use. We demonstrated the efficacy of THQ-Rosol for lymphatic mapping with in vitro and in vivo studies, wherein it revealed timely tumor drainage and afforded definitive lymph node visualization upon its administration and accumulation. THQ-Rosol serves as a proof-of-concept for the effective tailoring of an uncharged xanthene core-based scaffold/molecular platform toward a specific imaging application using rational design.
View details for PubMedID 30669835
- A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival AMER ASSOC CANCER RESEARCH. 2018
A novel theranostic strategy for MMP-14 expressing glioblastomas impacts survival.
Molecular cancer therapeutics
Glioblastoma (GBM) has a dismal prognosis. Evidence from preclinical tumor models and human trials indicates the role of GBM initiating cells (GIC) in GBM drug resistance. Here, we propose a new treatment option with tumor enzyme-activatable, combined therapeutic and diagnostic (theranostic) nanoparticles, which caused specific toxicity against GBM tumor cells and GICs. The theranostic cross-linked iron oxide nanoparticles (CLIO) were conjugated to a highly potent vascular disrupting agent (ICT) and secured with a matrix-metalloproteinase (MMP-14) cleavable peptide. Treatment with CLIO-ICT disrupted tumor vasculature of MMP-14 expressing GBM, induced GIC apoptosis and significantly impaired tumor growth. In addition, the iron core of CLIO-ICT enabled in vivo drug tracking with MR imaging. Treatment with CLIO-ICT plus temozolomide achieved tumor remission and significantly increased survival of human GBM bearing mice by more than 2 fold compared to treatment with temozolomide alone. Thus, we present a novel therapeutic strategy with significant impact on survival and great potential for clinical translation.
View details for PubMedID 28659432