Optical imaging in drug discovery and diagnostic applications

Licha, Kai; Olbrich, Carsten

doi:10.1016/j.addr.2005.01.021

Cited by 243 publications

(184 citation statements)

References 116 publications

Supporting

Mentioning

184

Contrasting

Order By: Relevance

“…The use of optical imaging techniques to monitor the biodistribution and target site accumulation of nanomedicine formulations has increased exponentially in recent years [41][42][43]. It is therefore highly important to be aware of some of the limitations associated with these techniques, including e.g.…”

Section: Optical Imaging Of Epr-mediated Passive Drug Targetingmentioning

confidence: 99%

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging

Theek

Gremse

Kunjachan

et al. 2014

Journal of Controlled Release

View full text Add to dashboard Cite

The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomographyfluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized nearinfrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5-12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4-11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, with in the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of <0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to preselecting patients likely to respond to passively tumor-targeted nanomedicine treatments. KeywordsDrug targeting; Nanomedicine; Theranostics; Cancer; EPR; HPMA; US; FMT; CT The biodistribution of nanomedicine formulations is very different from that of lowmolecular-weight drugs. As the size of nanocarrier materials generally is above the kidney clearance threshold (~5 nm), they tend to circulate for prolonged periods of time, and they are consequently able to exploit the fact that tumor blood vessels are more leaky that healthy blood vessels, resulting in passive, progressive and relatively selective accumulation at the pathological site over time. This phenomenon is known as the Enhanced Permeability and Retention (EPR) effect [7,8], and it is extensively used in drug delivery research. It is increasingly recognized, however, that EPR is a highly variably phenomenon, presenting not only with large differences between different animal models and patient tumors, but also with large inter-and intraindividual differences between tumors of the same sub-type. And even within a single tumor, certain vessels are significantly more leaky than others. Several recent reviews critically describe and comprehensively discuss the validity and the variability of the EPR effect [9][10][11][12][13][14]. To better understand EPR, to predict which animal models or patient tumors are likely to benefit from EPR-mediated passive drug targeting, and to thereby individualize and improve nano-chemotherapeutic treatments, it therefore seems highly important to identify imageable parameters to c...

show abstract

Section: Optical Imaging Of Epr-mediated Passive Drug Targetingmentioning

confidence: 99%

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging

Theek

Gremse

Kunjachan

et al. 2014

Journal of Controlled Release

View full text Add to dashboard Cite

show abstract

“…BLI, although only used in preclinical settings, is a cost-effective optical imaging modality (24,25). Because BLI output relies on ATP-dependent oxidation of D-luciferin by the endogenous luciferase of the cells, in vivo BLI is a reliable indicator of cell metabolic activity in real-time (26).…”

mentioning

confidence: 99%

PF-00477736 Mediates Checkpoint Kinase 1 Signaling Pathway and Potentiates Docetaxel-Induced Efficacy in Xenografts

Zhang¹,

Yan²,

Painter³

et al. 2009

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Checkpoint kinase 1 (Chk1) plays a critical role in the activation of mitotic spindle checkpoint and DNA damage checkpoint. We examined the preclinical use of the Chk1 inhibitor PF-00477736 as a docetaxel-sensitizing agent. Specifically, we investigated the correlation between PF-00477736^mediated modulation of biomarkers and the sensitization of docetaxel efficacy. Experimental Design: In vitro and in vivo studies using COLO205 and other cell lines were done to assess PF-00477736^induced enhancement of docetaxel efficacy and effects on associated biomarkers. Conclusions: Docetaxel triggers mitotic spindle checkpoint activation at low concentrations and activates both the DNA damage checkpoint and the spindle checkpoint at high concentrations. In combination with docetaxel, PF-00477736 abrogates the mitotic checkpoint, as well as the DNA damage checkpoint, and results in sensitization to docetaxel. Chk1inhibitor PF-00477736 offers a therapeutic potential for the enhancement of taxane therapy.

show abstract

“…[16][17][18][19][20][21][22][23][24][25] FRI is generally considered to be an excellent tool for monitoring nanomedicine accumulation in superficial tissues, such as subcutaneously inoculated tumors, but it is unable to provide quantitative information, and it also does not allow for the assessment of nanomedicine accumulation in deeper-seated tissues. 26 This means that it can be used for qualitative and comparative analyses, in which e.g.…”

mentioning

confidence: 99%

Noninvasive Optical Imaging of Nanomedicine Biodistribution

et al. 2012

View full text Add to dashboard Cite

Nanomedicines are submicrometer-sized carrier materials designed to improve the biodistribution of i.v. administered (chemo-) therapeutic agents. In recent years, ever more efforts in the nanomedicine field have employed optical imaging (OI) techniques to monitor biodistribution and target site accumulation. Thus far, however, the longitudinal assessment of nanomedicine biodistribution using OI has been impossible, due to limited light penetration (in case of 2D fluorescence reflectance imaging; FRI), and to the inability to accurately allocate fluorescent signals to non-superficial organs (in case of 3D fluorescence molecular tomography; FMT). Using a combination of high-resolution micro-computed tomography (μCT) and FMT, we have here set out to establish a hybrid imaging protocol for non-invasively visualizing and quantifying the accumulation of near-infrared fluorophore-labeled nanomedicines in tissues other than superficial tumors. To this end, HPMA-based polymeric drug carriers were labeled with Dy750, their biodistribution and tumor accumulation were analyzed using FMT, and the resulting data sets were fused with anatomical μCT data sets in which several different physiologically relevant organs were pre-segmented. The robustness of 3D organ segmentation was validated, and the results obtained using 3D CT-FMT were compared to those obtained upon standard 3D FMT and 2D FRI. Our findings convincingly demonstrate that combining anatomical μCT with molecular FMT facilitates the non-invasive assessment of nanomedicine biodistribution. KeywordsNanomedicine; Drug targeting; Biodistribution; FMT; FRI; CT Nanomedicines aim to deliver drugs and imaging agents more efficiently and more specifically to pathological sites. A significant amount of evidence has been obtained over the years exemplifying the superiority of nanomedicine formulations over free drugs, both at the preclinical and at the clinical level. [1][2][3][4][5] Prototypic examples of nanomedicine formulations are liposomes, polymers, micelles and nanoparticles. These submicrometersized carrier materials are designed to modulate the pharmacokinetics and the biodistribution of conjugated or entrapped (chemo-) therapeutic drugs. Upon intravenous (i.v.)

show abstract

Optical imaging in drug discovery and diagnostic applications

Cited by 243 publications

References 116 publications

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging

Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging

PF-00477736 Mediates Checkpoint Kinase 1 Signaling Pathway and Potentiates Docetaxel-Induced Efficacy in Xenografts

Noninvasive Optical Imaging of Nanomedicine Biodistribution

Contact Info

Product

Resources

About