{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["64(12)"],"submitter":["Watabe T"],"pubmed_abstract":["Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with <sup>89</sup>Zr or <sup>211</sup>At as a theranostic target in pancreatic ductal adenocarcinoma. <b>Methods:</b> GPC1 mAb clone 01a033 was labeled with <sup>89</sup>Zr or <sup>211</sup>At with a deferoxamine or decaborane linker, respectively. The internalization ability of GPC1 mAb was evaluated by fluorescence conjugation using a confocal microscope. PANC-1 xenograft mice (<i>n</i> = 6) were intravenously administered [<sup>89</sup>Zr]GPC1 mAb (0.91 ± 0.10 MBq), and PET/CT scanning was performed for 7 d. Uptake specificity was confirmed through a comparative study using GPC1-positive (BxPC-3) and GPC1-negative (BxPC-3 GPC1-knockout) xenografts (each <i>n</i> = 3) and a blocking study. DNA double-strand breaks were evaluated using the γH2AX antibody. The antitumor effect was evaluated by administering [<sup>211</sup>At]GPC1 mAb (∼100 kBq) to PANC-1 xenograft mice (<i>n</i> = 10). <b>Results:</b> GPC1 mAb clone 01a033 showed increased internalization ratios over time. One day after administration, a high accumulation of [<sup>89</sup>Zr]GPC1 mAb was observed in the PANC-1 xenograft (SUV<sub>max</sub>, 3.85 ± 0.10), which gradually decreased until day 7 (SUV<sub>max</sub>, 2.16 ± 0.30). The uptake in the BxPC-3 xenograft was significantly higher than in the BxPC-3 GPC1-knockout xenograft (SUV<sub>max</sub>, 4.66 ± 0.40 and 2.36 ± 0.36, respectively; <i>P</i> = 0.05). The uptake was significantly inhibited in the blocking group compared with the nonblocking group (percentage injected dose per gram, 7.3 ± 1.3 and 12.4 ± 3.0, respectively; <i>P</i> = 0.05). DNA double-strand breaks were observed by adding 150 kBq of [<sup>211</sup>At]GPC1 and were significantly suppressed by the internalization inhibitor (dynasore), suggesting a substantial contribution of the internalization ability to the antitumor effect. Tumor growth suppression was observed in PANC-1 mice after the administration of [<sup>211</sup>At]GPC1 mAb. Internalization inhibitors (prochlorperazine) significantly inhibited the therapeutic effect of [<sup>211</sup>At]GPC1 mAb, suggesting an essential role in targeted α-therapy. <b>Conclusion:</b> [<sup>89</sup>Zr]GPC1 mAb PET showed high tumoral uptake in the early phase after administration, and targeted α-therapy using [<sup>211</sup>At]GPC1 mAb showed tumor growth suppression. GPC1 is a promising target for future applications for the precise diagnosis of pancreatic ductal adenocarcinoma and GPC1-targeted theranostics."],"journal":["Journal of nuclear medicine : official publication, Society of Nuclear Medicine"],"pagination":["1949-1955"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10690121"],"repository":["biostudies-literature"],"pubmed_title":["Immuno-PET and Targeted α-Therapy Using Anti-Glypican-1 Antibody Labeled with <sup>89</sup>Zr or <sup>211</sup>At: A Theranostic Approach for Pancreatic Ductal Adenocarcinoma."],"pmcid":["PMC10690121"],"pubmed_authors":["Haba H","Shimosegawa E","Toyoshima A","Kobayashi T","Fukase K","Yamamoto R","Kaneda K","Serada S","Tomiyama N","Watabe T","Kurimoto K","Kabayama K","Wang Y","Ooe K","Naka S","Naka T"],"additional_accession":[]},"is_claimable":false,"name":"Immuno-PET and Targeted α-Therapy Using Anti-Glypican-1 Antibody Labeled with <sup>89</sup>Zr or <sup>211</sup>At: A Theranostic Approach for Pancreatic Ductal Adenocarcinoma.","description":"Glypican-1 (GPC1) is overexpressed in several solid cancers and is associated with tumor progression, whereas its expression is low in normal tissues. This study aimed to evaluate the potential of an anti-GPC1 monoclonal antibody (GPC1 mAb) labeled with <sup>89</sup>Zr or <sup>211</sup>At as a theranostic target in pancreatic ductal adenocarcinoma. <b>Methods:</b> GPC1 mAb clone 01a033 was labeled with <sup>89</sup>Zr or <sup>211</sup>At with a deferoxamine or decaborane linker, respectively. The internalization ability of GPC1 mAb was evaluated by fluorescence conjugation using a confocal microscope. PANC-1 xenograft mice (<i>n</i> = 6) were intravenously administered [<sup>89</sup>Zr]GPC1 mAb (0.91 ± 0.10 MBq), and PET/CT scanning was performed for 7 d. Uptake specificity was confirmed through a comparative study using GPC1-positive (BxPC-3) and GPC1-negative (BxPC-3 GPC1-knockout) xenografts (each <i>n</i> = 3) and a blocking study. DNA double-strand breaks were evaluated using the γH2AX antibody. The antitumor effect was evaluated by administering [<sup>211</sup>At]GPC1 mAb (∼100 kBq) to PANC-1 xenograft mice (<i>n</i> = 10). <b>Results:</b> GPC1 mAb clone 01a033 showed increased internalization ratios over time. One day after administration, a high accumulation of [<sup>89</sup>Zr]GPC1 mAb was observed in the PANC-1 xenograft (SUV<sub>max</sub>, 3.85 ± 0.10), which gradually decreased until day 7 (SUV<sub>max</sub>, 2.16 ± 0.30). The uptake in the BxPC-3 xenograft was significantly higher than in the BxPC-3 GPC1-knockout xenograft (SUV<sub>max</sub>, 4.66 ± 0.40 and 2.36 ± 0.36, respectively; <i>P</i> = 0.05). The uptake was significantly inhibited in the blocking group compared with the nonblocking group (percentage injected dose per gram, 7.3 ± 1.3 and 12.4 ± 3.0, respectively; <i>P</i> = 0.05). DNA double-strand breaks were observed by adding 150 kBq of [<sup>211</sup>At]GPC1 and were significantly suppressed by the internalization inhibitor (dynasore), suggesting a substantial contribution of the internalization ability to the antitumor effect. Tumor growth suppression was observed in PANC-1 mice after the administration of [<sup>211</sup>At]GPC1 mAb. Internalization inhibitors (prochlorperazine) significantly inhibited the therapeutic effect of [<sup>211</sup>At]GPC1 mAb, suggesting an essential role in targeted α-therapy. <b>Conclusion:</b> [<sup>89</sup>Zr]GPC1 mAb PET showed high tumoral uptake in the early phase after administration, and targeted α-therapy using [<sup>211</sup>At]GPC1 mAb showed tumor growth suppression. GPC1 is a promising target for future applications for the precise diagnosis of pancreatic ductal adenocarcinoma and GPC1-targeted theranostics.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Dec","modification":"2025-04-25T17:33:22.57Z","creation":"2025-04-06T04:05:20.996Z"},"accession":"S-EPMC10690121","cross_references":{"pubmed":["37827841"],"doi":["10.2967/jnumed.123.266313"]}}