Preclinical evaluation of 89Zr-labeled human antitransferrin receptor monoclonal antibody as a PET probe using a pancreatic cancer mouse model. Issue 3 (March 2015)

• Record Type: Journal Article
• Authors: Sugyo, Aya; Tsuji, Atsushi B.; Sudo, Hitomi; Nagatsu, Kotaro; Koizumi, Mitsuru; Ukai, Yoshinori; Kurosawa, Gene; Zhang, Ming-Rong; Kurosawa, Yoshikazu; Saga, Tsuneo
• Is Part Of: Nuclear medicine communications. Volume 36:Issue 3(2015:Mar.)
• Publication Date: 2015-03
• Subjects: Nuclear medicine -- Periodicals; 616.07575
• DOI: 10.1097/MNM.0000000000000245
• Languages: English
• ISSNs: 0143-3636

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objective</title> <p>Pancreatic cancer is aggressive and its prognosis remains poor; thus, effective therapy is urgently needed. Transferrin receptor (TfR) is highly expressed in pancreatic cancer and is considered to be a good candidate for molecular-targeted therapy. We radiolabeled and evaluated fully human anti-TfR monoclonal antibodies as a new PET probe for evaluating the biodistribution of the anti-TfR antibody in pancreatic cancer.</p> </sec> <sec> <title>Materials and methods</title> <p>TfR expression was evaluated in four human pancreatic cancer (MIAPaCa-2, PANC-1, BxPC-3, and AsPC-1) and murine A4 cell lines. The binding of <sup>125</sup>I-labeled anti-TfR antibodies (TSP-A01, TSP-A02, TSP-A03, and TSP-A04) to MIAPaCa-2 cells was compared. <sup>125</sup>I-labeled, <sup>67</sup>Ga-labeled, and <sup>89</sup>Zr-labeled TSP-A01 were evaluated by cell binding, competitive inhibition, and internalization assays. Biodistribution studies of <sup>125</sup>I-labeled and <sup>89</sup>Zr-labeled TSP-A01 were conducted in mice bearing MIAPaCa-2 and A4 tumors. PET imaging with [<sup>89</sup>Zr]TSP-A01 was carried out.</p> </sec> <sec> <title>Results</title> <p>MIAPaCa-2 cells showed the highest TfR expression <italic>in vitro</italic> and <italic>in vivo</italic>, whereas A4 cells showed no expression. Of the four antibodies, [<sup>125</sup>I]TSP-A01 showed the highest binding to MIAPaCa-2 cells, but not to A4 cells. The dissociation constant of TSP-A01 was 0.29 nmol/l. Uptake of radiolabeled TSP-A01, especially [<sup>89</sup>Zr]TSP-A01, was significantly higher in MIAPaCa-2 tumors than in A4 tumors. PET with [<sup>89</sup>Zr]TSP-A01 clearly visualized MIAPaCa-2 xenografts but not A4 xenografts.</p> </sec> <sec> <title>Conclusion</title> <p>[<sup>89</sup>Zr]TSP-A01 is a promising PET probe for evaluating the accumulation of anti-TfR antibody in pancreatic cancer and has the potential to facilitate the selection of appropriate patients who would benefit from anti-TfR antibody therapy.</p> </sec> </abstract>