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Near‑infrared fluorescence imaging of prostate cancer using heptamethine carbocyanine dyes.

Yuan J, Yi X, Yan F, Wang F, Qin W, Wu G, Yang X, Shao C, Chung LW - Mol Med Rep (2014)

Bottom Line: A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR‑783 and its derivative MHI‑148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities.Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17β‑estradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide.The results of the present study demonstrated that NIRF dye‑mediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

ABSTRACT
Near‑infrared fluorescence (NIRF) imaging is an attractive novel modality for the detection of cancer. A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR‑783 and its derivative MHI‑148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities. To investigate the feasibility of NIRF dye‑mediated prostate cancer imaging, dye uptake and subcellular co‑localization were investigated in PC‑3, DU‑145 and LNCaP human prostate cancer cells and RWPE‑1 normal prostate epithelial cells. Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17β‑estradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide. NIRF dyes were also used for the simulated detection of circulating tumor cells and the rapid detection of prostate cancer in human prostate cancer tissues and prostate cancer xenografts in mouse models. The results revealed that the cancer‑specific uptake of these organic dyes in prostate cancer cells occurred primarily via OATP1B3. A strong NIRF signal was detected in prostate cancer tissues, but not in normal tissues that were stained with IR‑783. Prostate cancer cells were recognized with particular NIR fluorescence in isolated mononuclear cell mixtures. The results of the present study demonstrated that NIRF dye‑mediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.

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Near-infrared fluorescence (NIRF) imaging of prostate cancer xenografts in a subcutaneous mice model using IR-783. (A) Representative in vivo near infrared fluorescence images of subcutaneous prostate cancer (from left to right: NIRF image, bright light image and superimposition). Two clear tumors were identified. (B) Frozen sections of the retrieved xenografts were stained with DAPI and observed under a confocal microscope (magnification, ×200). (C) Bio-distribution of IR-783 in the organs of nude mice bearing prostate cancer. The top row of images show the following from upper left to lower right: tumor, tumor, heart, liver, pancreas, spleen, lung, kidney, kidney, bladder. Bottom row: the whole intestine. (D) Tumors were confirmed by hematoxylin and eosin staining (magnification, ×200).
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f6-mmr-11-02-0821: Near-infrared fluorescence (NIRF) imaging of prostate cancer xenografts in a subcutaneous mice model using IR-783. (A) Representative in vivo near infrared fluorescence images of subcutaneous prostate cancer (from left to right: NIRF image, bright light image and superimposition). Two clear tumors were identified. (B) Frozen sections of the retrieved xenografts were stained with DAPI and observed under a confocal microscope (magnification, ×200). (C) Bio-distribution of IR-783 in the organs of nude mice bearing prostate cancer. The top row of images show the following from upper left to lower right: tumor, tumor, heart, liver, pancreas, spleen, lung, kidney, kidney, bladder. Bottom row: the whole intestine. (D) Tumors were confirmed by hematoxylin and eosin staining (magnification, ×200).

Mentions: Subcutaneous, intraosseous and orthotopical models of prostate cancer using athymic nude mice were established to validate the possible in vivo applications of NIRF imaging for the detection and observation of prostate cancer cells. NIRF dyes were administered and, 24 h later, high signal to background ratios were observed between the xenografts and the mouse models (Fig. 6). Bio-distribution analysis indicated that the metabolism of the NIRF dye was primarily through the excretions of bile, urine and feces. Furthermore, the NIRF signal from the prostate cancer cells remained detectable for >1 week. In sections of the xenografts retrieved from the sacrificed mice, the presence of prostate cancer cells and cancer specific uptake of NIRF dyes was confirmed.


Near‑infrared fluorescence imaging of prostate cancer using heptamethine carbocyanine dyes.

Yuan J, Yi X, Yan F, Wang F, Qin W, Wu G, Yang X, Shao C, Chung LW - Mol Med Rep (2014)

Near-infrared fluorescence (NIRF) imaging of prostate cancer xenografts in a subcutaneous mice model using IR-783. (A) Representative in vivo near infrared fluorescence images of subcutaneous prostate cancer (from left to right: NIRF image, bright light image and superimposition). Two clear tumors were identified. (B) Frozen sections of the retrieved xenografts were stained with DAPI and observed under a confocal microscope (magnification, ×200). (C) Bio-distribution of IR-783 in the organs of nude mice bearing prostate cancer. The top row of images show the following from upper left to lower right: tumor, tumor, heart, liver, pancreas, spleen, lung, kidney, kidney, bladder. Bottom row: the whole intestine. (D) Tumors were confirmed by hematoxylin and eosin staining (magnification, ×200).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262509&req=5

f6-mmr-11-02-0821: Near-infrared fluorescence (NIRF) imaging of prostate cancer xenografts in a subcutaneous mice model using IR-783. (A) Representative in vivo near infrared fluorescence images of subcutaneous prostate cancer (from left to right: NIRF image, bright light image and superimposition). Two clear tumors were identified. (B) Frozen sections of the retrieved xenografts were stained with DAPI and observed under a confocal microscope (magnification, ×200). (C) Bio-distribution of IR-783 in the organs of nude mice bearing prostate cancer. The top row of images show the following from upper left to lower right: tumor, tumor, heart, liver, pancreas, spleen, lung, kidney, kidney, bladder. Bottom row: the whole intestine. (D) Tumors were confirmed by hematoxylin and eosin staining (magnification, ×200).
Mentions: Subcutaneous, intraosseous and orthotopical models of prostate cancer using athymic nude mice were established to validate the possible in vivo applications of NIRF imaging for the detection and observation of prostate cancer cells. NIRF dyes were administered and, 24 h later, high signal to background ratios were observed between the xenografts and the mouse models (Fig. 6). Bio-distribution analysis indicated that the metabolism of the NIRF dye was primarily through the excretions of bile, urine and feces. Furthermore, the NIRF signal from the prostate cancer cells remained detectable for >1 week. In sections of the xenografts retrieved from the sacrificed mice, the presence of prostate cancer cells and cancer specific uptake of NIRF dyes was confirmed.

Bottom Line: A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR‑783 and its derivative MHI‑148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities.Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17β‑estradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide.The results of the present study demonstrated that NIRF dye‑mediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.

ABSTRACT
Near‑infrared fluorescence (NIRF) imaging is an attractive novel modality for the detection of cancer. A previous study defined two organic polymethine cyanine dyes as ideal NIRF probes, IR‑783 and its derivative MHI‑148, which have excellent optical characteristics, superior biocompatibility and cancer targeting abilities. To investigate the feasibility of NIRF dye‑mediated prostate cancer imaging, dye uptake and subcellular co‑localization were investigated in PC‑3, DU‑145 and LNCaP human prostate cancer cells and RWPE‑1 normal prostate epithelial cells. Different organic anion transporting peptide (OATP) inhibitors were utilized to explore the potential role of the OATP subtype, including the nonspecific OATP inhibitor bromosulfophthalein, the OATP1 inhibitor 17β‑estradiol, the selective OATP1B1 inhibitor rifampicin and the selective OATP1B3 inhibitor cholecystokinin octapeptide. NIRF dyes were also used for the simulated detection of circulating tumor cells and the rapid detection of prostate cancer in human prostate cancer tissues and prostate cancer xenografts in mouse models. The results revealed that the cancer‑specific uptake of these organic dyes in prostate cancer cells occurred primarily via OATP1B3. A strong NIRF signal was detected in prostate cancer tissues, but not in normal tissues that were stained with IR‑783. Prostate cancer cells were recognized with particular NIR fluorescence in isolated mononuclear cell mixtures. The results of the present study demonstrated that NIRF dye‑mediated imaging is a feasible and practicable method for prostate cancer detection, although further investigative studies are required before clinical translation.

Show MeSH
Related in: MedlinePlus