Anti‑tissue factor antibody‑mediated immuno‑SPECT imaging of tissue factor expression in mouse models of pancreatic cancer

Sugyo,Aya; Aung,Winn; Tsuji,Atsushi   B.; Sudo,Hitomi; Takashima,Hiroki; Yasunaga,Masahiro; Matsumura,Yasuhiro; Saga,Tsuneo; Higashi,Tatsuya

doi:10.3892/or.2019.7017

Anti‑tissue factor antibody‑mediated immuno‑SPECT imaging of tissue factor expression in mouse models of pancreatic cancer

Authors:
- Aya Sugyo
- Winn Aung
- Atsushi B. Tsuji
- Hitomi Sudo
- Hiroki Takashima
- Masahiro Yasunaga
- Yasuhiro Matsumura
- Tsuneo Saga
- Tatsuya Higashi
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Affiliations: Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology (QST‑NIRS), Inage, Chiba 263‑8555, Japan, Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277‑8577, Japan, Department of Diagnostic Radiology, Kyoto University Hospital, Sakyo‑ku, Kyoto 606‑8507, Japan
Published online on: February 14, 2019 https://doi.org/10.3892/or.2019.7017
Pages: 2371-2378

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Abstract

Tissue factor (TF) has emerged as a critical factor in oncogenic events, leading to the development of TF‑targeted diagnostic and therapeutic approaches. A non‑invasive imaging method to evaluate target molecule expression with high sensitivity and high quantitative ability is imperative for selecting the appropriate patients for TF‑targeted therapy. To elucidate the potential of 111In‑labeled anti‑TF antibody 1849 (111In‑1849) as an immuno‑single photon emission computed tomography (SPECT) probe targeting TF, we evaluated TF‑dependent in vitro binding as well as in vivo biodistribution and tumor accumulation of 111In‑1849 in pancreatic cancer cells/models with varying TF expression levels. TF expression levels in five human pancreatic cancer cell lines, BxPC‑3, BxPC‑3‑TF‑knockout (BxPC‑3‑TFKO), Capan‑1, PSN‑1 and SUIT‑2, were examined by immunofluorescence. Binding of 111In‑1849 to each cell line was assessed. Biodistribution and imaging studies were also conducted in tumor‑bearing mice. Furthermore, the relationship of TF expression with cell binding and tumor uptake was analyzed. In the immunofluorescence studies, BxPC‑3 exhibited the highest TF expression, followed by Capan‑1, PSN‑1, SUIT‑2 and BxPC‑3‑TFKO. Cell binding assays revealed that BxPC‑3 cells had the highest 111In‑1849 binding, followed by PSN‑1, Capan‑1 and SUIT‑2; no binding was detected in BxPC‑3‑TFKO cells. The BxPC‑3 xenograft was clearly visualized on 111In‑1849 SPECT/CT, and the highest uptake was detected on day 4. The biodistribution of 111In‑1849 on day 4 revealed that tumor uptake ranged from 8.68 to 50.58% of the injected dose per gram of tissue; BxPC‑3 had the highest uptake and SUIT‑2 had the lowest. TF expression was significantly associated with cell binding (R2=0.79, P<0.05) and tumor uptake (R2=0.92, P<0.01). The association of 111In‑1849 uptake with TF expression suggests the potential application of non‑invasive imaging with radiolabelled 1849 for selecting the appropriate patients who would likely respond to TF‑targeted therapies in clinical practice.

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