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Are quantum dots ready for in vivo imaging in human subjects?

Cai W, Hsu AR, Li ZB, Chen X - Nanoscale Res Lett (2007)

Bottom Line: Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability.For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases.With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting.

View Article: PubMed Central - PubMed

Affiliation: The Molecular Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484, USA.

ABSTRACT
Nanotechnology has the potential to profoundly transform the nature of cancer diagnosis and cancer patient management in the future. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology. QDs are fluorescent semiconductor nanoparticles suitable for multiplexed in vitro and in vivo imaging. Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability. For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases. In vivo targeted tumor imaging with biocompatible QDs has recently become possible in mouse models. With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting.

No MeSH data available.


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Dualfunctional QD-based probe for both PET and NIRF imaging. (a) PET image of harvested major organs/tissues at 5 h post-injection of the dualfunctional probe. (b) NIRF image of harvested major organs/tissues at 5 h post-injection of the probe. (c) Immunofluorescence staining of the tumor tissue revealed that QDs are targeting the tumor vasculature. From [207]
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Figure 13: Dualfunctional QD-based probe for both PET and NIRF imaging. (a) PET image of harvested major organs/tissues at 5 h post-injection of the dualfunctional probe. (b) NIRF image of harvested major organs/tissues at 5 h post-injection of the probe. (c) Immunofluorescence staining of the tumor tissue revealed that QDs are targeting the tumor vasculature. From [207]

Mentions: QDs have relatively large surface areas which can be conjugated with more than one targeting ligand. Novel tumor-specific antibody fragments, growth factors, peptides, and small molecules can be attached to QDs for the delivery of QDs to tumors in vivo for multi-parameter imaging of biomarkers, with the ultimate goal of guiding therapy selection and predicting response to therapy. This nano-platform approach will enable detection and measurement of many biomarkers simultaneously which may lead to better signal/contrast than QDs modified with only one type of targeting ligand. The ability to accurately assess the pharmacokinetics and tumor targeting efficacy of the biologically modified QDs is of crucial importance to assess future multitargeting (to target multiple targets with the same QD) and eventually multiplexing (to target multiple targets simultaneously using QDs of different emission wavelengths) studies. Dualmodality PET/NIRF imaging probe offers synergistic advantages over the single modality imaging probe by overcoming the difficulty of quantifying fluorescence intensity in vivo and ex vivo. For the first time, we quantitatively evaluated the tumor targeting efficacy of dualfunctional QD-based probes using both NIRF and PET imaging (Fig. 13) [207]. Both RGD peptides and macrocyclic chelator DOTA were conjugated to QD705. RGD peptides can allow for integrin αvβ3 targeting and DOTA can complex 64Cu (a positron emitter with 12.7 h half-life) to enable PET imaging [160,208,209]. Non-invasive PET imaging using radiolabeled QD conjugates can provide a robust and reliable measure of the in vivo biodistribution of QDs. With further improvement in QD technology, it is expected that accurate evaluation of the in vivo tumor targeting efficacy using quantitative imaging modalities (e.g. PET) will greatly facilitate future biomedical applications of QDs. Such information will also be critical for fluorescence-guided surgery by sensitive, specific, and real-time intraoperative visualization of molecular features of normal and disease processes.


Are quantum dots ready for in vivo imaging in human subjects?

Cai W, Hsu AR, Li ZB, Chen X - Nanoscale Res Lett (2007)

Dualfunctional QD-based probe for both PET and NIRF imaging. (a) PET image of harvested major organs/tissues at 5 h post-injection of the dualfunctional probe. (b) NIRF image of harvested major organs/tissues at 5 h post-injection of the probe. (c) Immunofluorescence staining of the tumor tissue revealed that QDs are targeting the tumor vasculature. From [207]
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Related In: Results  -  Collection

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Figure 13: Dualfunctional QD-based probe for both PET and NIRF imaging. (a) PET image of harvested major organs/tissues at 5 h post-injection of the dualfunctional probe. (b) NIRF image of harvested major organs/tissues at 5 h post-injection of the probe. (c) Immunofluorescence staining of the tumor tissue revealed that QDs are targeting the tumor vasculature. From [207]
Mentions: QDs have relatively large surface areas which can be conjugated with more than one targeting ligand. Novel tumor-specific antibody fragments, growth factors, peptides, and small molecules can be attached to QDs for the delivery of QDs to tumors in vivo for multi-parameter imaging of biomarkers, with the ultimate goal of guiding therapy selection and predicting response to therapy. This nano-platform approach will enable detection and measurement of many biomarkers simultaneously which may lead to better signal/contrast than QDs modified with only one type of targeting ligand. The ability to accurately assess the pharmacokinetics and tumor targeting efficacy of the biologically modified QDs is of crucial importance to assess future multitargeting (to target multiple targets with the same QD) and eventually multiplexing (to target multiple targets simultaneously using QDs of different emission wavelengths) studies. Dualmodality PET/NIRF imaging probe offers synergistic advantages over the single modality imaging probe by overcoming the difficulty of quantifying fluorescence intensity in vivo and ex vivo. For the first time, we quantitatively evaluated the tumor targeting efficacy of dualfunctional QD-based probes using both NIRF and PET imaging (Fig. 13) [207]. Both RGD peptides and macrocyclic chelator DOTA were conjugated to QD705. RGD peptides can allow for integrin αvβ3 targeting and DOTA can complex 64Cu (a positron emitter with 12.7 h half-life) to enable PET imaging [160,208,209]. Non-invasive PET imaging using radiolabeled QD conjugates can provide a robust and reliable measure of the in vivo biodistribution of QDs. With further improvement in QD technology, it is expected that accurate evaluation of the in vivo tumor targeting efficacy using quantitative imaging modalities (e.g. PET) will greatly facilitate future biomedical applications of QDs. Such information will also be critical for fluorescence-guided surgery by sensitive, specific, and real-time intraoperative visualization of molecular features of normal and disease processes.

Bottom Line: Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability.For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases.With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting.

View Article: PubMed Central - PubMed

Affiliation: The Molecular Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University School of Medicine, 1201 Welch Rd, P095, Stanford, CA 94305-5484, USA.

ABSTRACT
Nanotechnology has the potential to profoundly transform the nature of cancer diagnosis and cancer patient management in the future. Over the past decade, quantum dots (QDs) have become one of the fastest growing areas of research in nanotechnology. QDs are fluorescent semiconductor nanoparticles suitable for multiplexed in vitro and in vivo imaging. Numerous studies on QDs have resulted in major advancements in QD surface modification, coating, biocompatibility, sensitivity, multiplexing, targeting specificity, as well as important findings regarding toxicity and applicability. For in vitro applications, QDs can be used in place of traditional organic fluorescent dyes in virtually any system, outperforming organic dyes in the majority of cases. In vivo targeted tumor imaging with biocompatible QDs has recently become possible in mouse models. With new advances in QD technology such as bioluminescence resonance energy transfer, synthesis of smaller size non-Cd based QDs, improved surface coating and conjugation, and multifunctional probes for multimodality imaging, it is likely that human applications of QDs will soon be possible in a clinical setting.

No MeSH data available.


Related in: MedlinePlus