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A novel PET imaging using ⁶⁴Cu-labeled monoclonal antibody against mesothelin commonly expressed on cancer cells.

Kobayashi K, Sasaki T, Takenaka F, Yakushiji H, Fujii Y, Kishi Y, Kita S, Shen L, Kumon H, Matsuura E - J Immunol Res (2015)

Bottom Line: Mesothelin (MSLN) is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum.Clone 11-25 is a murine hybridoma secreting monoclonal antibody (mAb) against human MSLN.In in vitro and ex vivo immunochemical studies, we demonstrated specificity of 11-25 mAb to membranous MSLN expressed on several pancreatic cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan ; Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.

ABSTRACT
Mesothelin (MSLN) is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum. Clone 11-25 is a murine hybridoma secreting monoclonal antibody (mAb) against human MSLN. In this study, we applied the 11-25 mAb to in vivo imaging to detect MSLN-expressing tumors. In in vitro and ex vivo immunochemical studies, we demonstrated specificity of 11-25 mAb to membranous MSLN expressed on several pancreatic cancer cells. We showed the accumulation of Alexa Fluor 750-labeled 11-25 mAb in MSLN-expressing tumor xenografts in athymic nude mice. Then, 11-25 mAb was labeled with (64)Cu via a chelating agent DOTA and was used in both in vitro cell binding assay and in vivo positron emission tomography (PET) imaging in the tumor-bearing mice. We confirmed that (64)Cu-labeled 11-25 mAb highly accumulated in MSLN-expressing tumors as compared to MSLN-negative ones. The (64)Cu-labeled 11-25 mAb is potentially useful as a PET probe capable of being used for wide range of tumors, rather than (18)F-FDG that occasionally provides nonspecific accumulation into the inflammatory lesions.

No MeSH data available.


Related in: MedlinePlus

In vivo and ex vivo NIR optical imaging by Alexa Fluor 750-labeled 11-25 mAb. (a) Alexa Fluor 750-labeled 11-25 mAb (90 μg/mouse) was administered to mice bearing BxPC-3 and PANC-1 intravenously. Alexa Fluor 750 fluorescence was then monitored by IVIS-200 imaging system 24, 48, and 72 hours after the injection. The minimum and maximum values of the photon gage are shown under each photograph. (b) 24 hours after administration of Alexa Fluor 750-labeled 11-25 mAb, tumors were dissected from mice and ex vivo fluorescence images were taken.
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fig3: In vivo and ex vivo NIR optical imaging by Alexa Fluor 750-labeled 11-25 mAb. (a) Alexa Fluor 750-labeled 11-25 mAb (90 μg/mouse) was administered to mice bearing BxPC-3 and PANC-1 intravenously. Alexa Fluor 750 fluorescence was then monitored by IVIS-200 imaging system 24, 48, and 72 hours after the injection. The minimum and maximum values of the photon gage are shown under each photograph. (b) 24 hours after administration of Alexa Fluor 750-labeled 11-25 mAb, tumors were dissected from mice and ex vivo fluorescence images were taken.

Mentions: To analyze the in vivo distribution of 11-25 mAb by fluorescence imaging, Alexa Fluor 750-labeled 11-25 mAb was administered to mice bearing BxPC-3 and PANC-1 tumors, and in vivo imaging was conducted with IVIS 200. Figure 3 shows the result of NIRF imaging. At 24 hours after injection, fluorescence from Alexa Fluor 750-labeled 11-25 mAb was detected throughout the body of the animal; however, MSLN-positive BxPC-3 xenograft gave off brighter fluorescence than its neighborhood did. Furthermore, time-dependent accumulation of fluorescence to BxPC-3 tumor xenografts was observed and fluorescence in other parts was cleared gradually. At 72 hours after injection, significant fluorescence strength was detected mainly in the BxPC-3 tumor xenograft. Figure 3(b) shows the ex vivo image of the dissected tumor xenograft of another mouse treated in the same way at 24 hours after injection. BxPC-3 xenograft showed rather strong fluorescence as compared with the PANC-1 xenograft.


A novel PET imaging using ⁶⁴Cu-labeled monoclonal antibody against mesothelin commonly expressed on cancer cells.

Kobayashi K, Sasaki T, Takenaka F, Yakushiji H, Fujii Y, Kishi Y, Kita S, Shen L, Kumon H, Matsuura E - J Immunol Res (2015)

In vivo and ex vivo NIR optical imaging by Alexa Fluor 750-labeled 11-25 mAb. (a) Alexa Fluor 750-labeled 11-25 mAb (90 μg/mouse) was administered to mice bearing BxPC-3 and PANC-1 intravenously. Alexa Fluor 750 fluorescence was then monitored by IVIS-200 imaging system 24, 48, and 72 hours after the injection. The minimum and maximum values of the photon gage are shown under each photograph. (b) 24 hours after administration of Alexa Fluor 750-labeled 11-25 mAb, tumors were dissected from mice and ex vivo fluorescence images were taken.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4390102&req=5

fig3: In vivo and ex vivo NIR optical imaging by Alexa Fluor 750-labeled 11-25 mAb. (a) Alexa Fluor 750-labeled 11-25 mAb (90 μg/mouse) was administered to mice bearing BxPC-3 and PANC-1 intravenously. Alexa Fluor 750 fluorescence was then monitored by IVIS-200 imaging system 24, 48, and 72 hours after the injection. The minimum and maximum values of the photon gage are shown under each photograph. (b) 24 hours after administration of Alexa Fluor 750-labeled 11-25 mAb, tumors were dissected from mice and ex vivo fluorescence images were taken.
Mentions: To analyze the in vivo distribution of 11-25 mAb by fluorescence imaging, Alexa Fluor 750-labeled 11-25 mAb was administered to mice bearing BxPC-3 and PANC-1 tumors, and in vivo imaging was conducted with IVIS 200. Figure 3 shows the result of NIRF imaging. At 24 hours after injection, fluorescence from Alexa Fluor 750-labeled 11-25 mAb was detected throughout the body of the animal; however, MSLN-positive BxPC-3 xenograft gave off brighter fluorescence than its neighborhood did. Furthermore, time-dependent accumulation of fluorescence to BxPC-3 tumor xenografts was observed and fluorescence in other parts was cleared gradually. At 72 hours after injection, significant fluorescence strength was detected mainly in the BxPC-3 tumor xenograft. Figure 3(b) shows the ex vivo image of the dissected tumor xenograft of another mouse treated in the same way at 24 hours after injection. BxPC-3 xenograft showed rather strong fluorescence as compared with the PANC-1 xenograft.

Bottom Line: Mesothelin (MSLN) is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum.Clone 11-25 is a murine hybridoma secreting monoclonal antibody (mAb) against human MSLN.In in vitro and ex vivo immunochemical studies, we demonstrated specificity of 11-25 mAb to membranous MSLN expressed on several pancreatic cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan ; Department of Urology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.

ABSTRACT
Mesothelin (MSLN) is a 40-kDa cell differentiation-associated glycoprotein appearing with carcinogenesis and is highly expressed in many human cancers, including the majority of pancreatic adenocarcinomas, ovarian cancers, and mesotheliomas, while its expression in normal tissue is limited to mesothelial cells lining the pleura, pericardium, and peritoneum. Clone 11-25 is a murine hybridoma secreting monoclonal antibody (mAb) against human MSLN. In this study, we applied the 11-25 mAb to in vivo imaging to detect MSLN-expressing tumors. In in vitro and ex vivo immunochemical studies, we demonstrated specificity of 11-25 mAb to membranous MSLN expressed on several pancreatic cancer cells. We showed the accumulation of Alexa Fluor 750-labeled 11-25 mAb in MSLN-expressing tumor xenografts in athymic nude mice. Then, 11-25 mAb was labeled with (64)Cu via a chelating agent DOTA and was used in both in vitro cell binding assay and in vivo positron emission tomography (PET) imaging in the tumor-bearing mice. We confirmed that (64)Cu-labeled 11-25 mAb highly accumulated in MSLN-expressing tumors as compared to MSLN-negative ones. The (64)Cu-labeled 11-25 mAb is potentially useful as a PET probe capable of being used for wide range of tumors, rather than (18)F-FDG that occasionally provides nonspecific accumulation into the inflammatory lesions.

No MeSH data available.


Related in: MedlinePlus