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In vivo fluorescence lifetime imaging monitors binding of specific probes to cancer biomarkers.

Ardeshirpour Y, Chernomordik V, Zielinski R, Capala J, Griffiths G, Vasalatiy O, Smirnov AV, Knutson JR, Lyakhov I, Achilefu S, Gandjbakhche A, Hassan M - PLoS ONE (2012)

Bottom Line: One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells.Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention.Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the "image and treat" concept, especially for early evaluation of the efficacy of the therapy.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the "image and treat" concept, especially for early evaluation of the efficacy of the therapy.

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Histological (IHC) images of tumor tissues for tumor with no HER2 expression (A–B) MDA-MB-468, and highly expressed HER2 tumor (C–D) BT-474 and (E–F) NCI-N87.Tumor tissue was extracted from animals 24 hours post HER2-Affibody-DyLight750 injection, fixed in 10%NBF and analyzed by IHC for detection of HER2 status (A,C and E) and Affibody presence (B,D and F).
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pone-0031881-g009: Histological (IHC) images of tumor tissues for tumor with no HER2 expression (A–B) MDA-MB-468, and highly expressed HER2 tumor (C–D) BT-474 and (E–F) NCI-N87.Tumor tissue was extracted from animals 24 hours post HER2-Affibody-DyLight750 injection, fixed in 10%NBF and analyzed by IHC for detection of HER2 status (A,C and E) and Affibody presence (B,D and F).

Mentions: The histological images of extracted tumor tissues 24 hours after injection for tumor with no HER2 expression (9A–9B) MDA-MB-468, and tumors with high HER2 expression (9C–9D) BT-474 and (9E–9F) NCI-N87 are provided in Fig. 9.


In vivo fluorescence lifetime imaging monitors binding of specific probes to cancer biomarkers.

Ardeshirpour Y, Chernomordik V, Zielinski R, Capala J, Griffiths G, Vasalatiy O, Smirnov AV, Knutson JR, Lyakhov I, Achilefu S, Gandjbakhche A, Hassan M - PLoS ONE (2012)

Histological (IHC) images of tumor tissues for tumor with no HER2 expression (A–B) MDA-MB-468, and highly expressed HER2 tumor (C–D) BT-474 and (E–F) NCI-N87.Tumor tissue was extracted from animals 24 hours post HER2-Affibody-DyLight750 injection, fixed in 10%NBF and analyzed by IHC for detection of HER2 status (A,C and E) and Affibody presence (B,D and F).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285647&req=5

pone-0031881-g009: Histological (IHC) images of tumor tissues for tumor with no HER2 expression (A–B) MDA-MB-468, and highly expressed HER2 tumor (C–D) BT-474 and (E–F) NCI-N87.Tumor tissue was extracted from animals 24 hours post HER2-Affibody-DyLight750 injection, fixed in 10%NBF and analyzed by IHC for detection of HER2 status (A,C and E) and Affibody presence (B,D and F).
Mentions: The histological images of extracted tumor tissues 24 hours after injection for tumor with no HER2 expression (9A–9B) MDA-MB-468, and tumors with high HER2 expression (9C–9D) BT-474 and (9E–9F) NCI-N87 are provided in Fig. 9.

Bottom Line: One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells.Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention.Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the "image and treat" concept, especially for early evaluation of the efficacy of the therapy.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.

ABSTRACT
One of the most important factors in choosing a treatment strategy for cancer is characterization of biomarkers in cancer cells. Particularly, recent advances in Monoclonal Antibodies (MAB) as primary-specific drugs targeting tumor receptors show that their efficacy depends strongly on characterization of tumor biomarkers. Assessment of their status in individual patients would facilitate selection of an optimal treatment strategy, and the continuous monitoring of those biomarkers and their binding process to the therapy would provide a means for early evaluation of the efficacy of therapeutic intervention. In this study we have demonstrated for the first time in live animals that the fluorescence lifetime can be used to detect the binding of targeted optical probes to the extracellular receptors on tumor cells in vivo. The rationale was that fluorescence lifetime of a specific probe is sensitive to local environment and/or affinity to other molecules. We attached Near-InfraRed (NIR) fluorescent probes to Human Epidermal Growth Factor 2 (HER2/neu)-specific Affibody molecules and used our time-resolved optical system to compare the fluorescence lifetime of the optical probes that were bound and unbound to tumor cells in live mice. Our results show that the fluorescence lifetime changes in our model system delineate HER2 receptor bound from the unbound probe in vivo. Thus, this method is useful as a specific marker of the receptor binding process, which can open a new paradigm in the "image and treat" concept, especially for early evaluation of the efficacy of the therapy.

Show MeSH
Related in: MedlinePlus