Preclinical evaluation of 89Zr-labeled human antitransferrin receptor monoclonal antibody as a PET probe using a pancreatic cancer mouse model

Aya Sugyo, Atsushi B. Tsuji, Hitomi Sudo, Kotaro Nagatsu, Mitsuru Koizumi, Yoshinori Ukai, Gene Kurosawa, Ming Rong Zhang, Yoshikazu Kurosawa, Tsuneo Saga

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

OBJECTIVE: 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. MATERIALS AND METHODS: 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 I-labeled anti-TfR antibodies (TSP-A01, TSP-A02, TSP-A03, and TSP-A04) to MIAPaCa-2 cells was compared. I-labeled, Ga-labeled, and Zr-labeled TSP-A01 were evaluated by cell binding, competitive inhibition, and internalization assays. Biodistribution studies of I-labeled and Zr-labeled TSP-A01 were conducted in mice bearing MIAPaCa-2 and A4 tumors. PET imaging with [Zr]TSP-A01 was carried out. RESULTS: MIAPaCa-2 cells showed the highest TfR expression in vitro and in vivo, whereas A4 cells showed no expression. Of the four antibodies, [I]TSP-A01 showed the highest binding to MIAPaCa-2 cells, but not to A4 cells. The dissociation constant of TSP-A01 was 0.29nmol/l. Uptake of radiolabeled TSP-A01, especially [Zr]TSP-A01, was significantly higher in MIAPaCa-2 tumors than in A4 tumors. PET with [Zr]TSP-A01 clearly visualized MIAPaCa-2 xenografts but not A4 xenografts. CONCLUSION: [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..

Original languageEnglish
Pages (from-to)286-294
Number of pages9
JournalNuclear medicine communications
Volume36
Issue number3
DOIs
Publication statusPublished - 06-03-2015

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

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