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Updated: Jan 28, 2026
Flow Cytometry Analysis of Tissue Factor Expression in Human Platelets
Published on: November 22, 2024
Anti‑tissue factor antibody‑mediated immuno‑SPECT imaging of tissue factor expression in mouse models of pancreatic
Aya Sugyo1, Winn Aung1, Atsushi B Tsuji1
1Department 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.
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.
Insights
This study shows that 111In-labeled anti-tissue factor (TF) antibody 1849 can non-invasively image TF expression in pancreatic cancer. This immuno-single photon emission computed tomography (SPECT) probe accurately reflects TF levels, aiding patient selection for TF-targeted therapies.
Area of Science:
- Oncology
- Radiochemistry
- Molecular Imaging
Background:
- Tissue factor (TF) is a key factor in cancer development and a target for therapies.
- Non-invasive imaging is crucial for patient selection in targeted cancer therapy.
- Developing sensitive and quantitative imaging probes for TF is essential.
Purpose of the Study:
- To evaluate 111In-labeled anti-TF antibody 1849 (111In-1849) as an immuno-single photon emission computed tomography (SPECT) probe for TF.
- To assess the in vitro binding and in vivo biodistribution of 111In-1849 in pancreatic cancer models with varying TF expression.
- To determine the correlation between TF expression levels and the probe's binding and tumor uptake.
Main Methods:
- Examined TF expression in five human pancreatic cancer cell lines using immunofluorescence.
- Assessed the binding of 111In-1849 to each cell line.
- Conducted biodistribution and SPECT/CT imaging studies in tumor-bearing mice.
Main Results:
- TF expression varied across cell lines, with BxPC-3 showing the highest levels.
- 111In-1849 binding correlated directly with TF expression, with no binding in TF-knockout cells.
- SPECT/CT imaging clearly visualized tumors, and in vivo uptake of 111In-1849 significantly correlated with TF expression (R2=0.92, P<0.01).
Conclusions:
- 111In-1849 demonstrates high TF-specific binding and tumor accumulation in pancreatic cancer models.
- The probe's uptake accurately reflects TF expression levels, validated by in vitro and in vivo studies.
- Non-invasive imaging with 111In-1849 has potential for selecting patients likely to respond to TF-targeted therapies.
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