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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

Representative PET images of mice bearing CFPAC-1, BxPC-3, and PANC-1. (a) A 3D volume rendering CT image of a mouse and a scheme showing the direction of PET images. The positions of xenografts and cross sections are shown on the CT image. CFPAC-1, BxPC-3, and PANC-1 xenografts were at the right shoulder, the left femur, and the right femur, respectively. (b) Serial PET/CT images of the nude mice at 0, 24, and 48 hours after administration of 64Cu-DOTA-11-25 mAb and (c) 64Cu-DOTA-anti-KLH mAb. Upper panels showed maximum intensity projections (MIP) of whole bodies. Lower panels are transverse PET/CT images at the position of tumors. Upper images (U) showed center of CFPAC-1 (CF), and lower images (L) showed BxPC-3 (Bx) and PANC-1 (P).
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fig7: Representative PET images of mice bearing CFPAC-1, BxPC-3, and PANC-1. (a) A 3D volume rendering CT image of a mouse and a scheme showing the direction of PET images. The positions of xenografts and cross sections are shown on the CT image. CFPAC-1, BxPC-3, and PANC-1 xenografts were at the right shoulder, the left femur, and the right femur, respectively. (b) Serial PET/CT images of the nude mice at 0, 24, and 48 hours after administration of 64Cu-DOTA-11-25 mAb and (c) 64Cu-DOTA-anti-KLH mAb. Upper panels showed maximum intensity projections (MIP) of whole bodies. Lower panels are transverse PET/CT images at the position of tumors. Upper images (U) showed center of CFPAC-1 (CF), and lower images (L) showed BxPC-3 (Bx) and PANC-1 (P).

Mentions: Figure 7 shows the representative result of the PET imaging. Figure 7(a) is the 3D volume rendering image of CT of the mouse and shows the position of xenografts and the position of the cross section. In the upper cross section images of Figure 7(b), high accumulation of 64Cu-DOTA-11-25 mAb was observed in the CFPAC-1 xenograft (red arrowhead) at 24 and 48 hours. In the lower cross section images, 64Cu-DOTA-11-25 accumulation was observed in the BxPC-3 xenograft (yellow arrowhead) but not in the PANC-1 xenograft (white arrowhead). On the other hand, the accumulation of 64Cu-DOTA-anti-KLH mAb in CFPAC-1 and BxPC-3 xenografts (Figure 7(c)) was lower than those of 64Cu-DOTA-11-25 mAb.


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)

Representative PET images of mice bearing CFPAC-1, BxPC-3, and PANC-1. (a) A 3D volume rendering CT image of a mouse and a scheme showing the direction of PET images. The positions of xenografts and cross sections are shown on the CT image. CFPAC-1, BxPC-3, and PANC-1 xenografts were at the right shoulder, the left femur, and the right femur, respectively. (b) Serial PET/CT images of the nude mice at 0, 24, and 48 hours after administration of 64Cu-DOTA-11-25 mAb and (c) 64Cu-DOTA-anti-KLH mAb. Upper panels showed maximum intensity projections (MIP) of whole bodies. Lower panels are transverse PET/CT images at the position of tumors. Upper images (U) showed center of CFPAC-1 (CF), and lower images (L) showed BxPC-3 (Bx) and PANC-1 (P).
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig7: Representative PET images of mice bearing CFPAC-1, BxPC-3, and PANC-1. (a) A 3D volume rendering CT image of a mouse and a scheme showing the direction of PET images. The positions of xenografts and cross sections are shown on the CT image. CFPAC-1, BxPC-3, and PANC-1 xenografts were at the right shoulder, the left femur, and the right femur, respectively. (b) Serial PET/CT images of the nude mice at 0, 24, and 48 hours after administration of 64Cu-DOTA-11-25 mAb and (c) 64Cu-DOTA-anti-KLH mAb. Upper panels showed maximum intensity projections (MIP) of whole bodies. Lower panels are transverse PET/CT images at the position of tumors. Upper images (U) showed center of CFPAC-1 (CF), and lower images (L) showed BxPC-3 (Bx) and PANC-1 (P).
Mentions: Figure 7 shows the representative result of the PET imaging. Figure 7(a) is the 3D volume rendering image of CT of the mouse and shows the position of xenografts and the position of the cross section. In the upper cross section images of Figure 7(b), high accumulation of 64Cu-DOTA-11-25 mAb was observed in the CFPAC-1 xenograft (red arrowhead) at 24 and 48 hours. In the lower cross section images, 64Cu-DOTA-11-25 accumulation was observed in the BxPC-3 xenograft (yellow arrowhead) but not in the PANC-1 xenograft (white arrowhead). On the other hand, the accumulation of 64Cu-DOTA-anti-KLH mAb in CFPAC-1 and BxPC-3 xenografts (Figure 7(c)) was lower than those of 64Cu-DOTA-11-25 mAb.

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