Sökning: WFRF:(Scheenen Tom W.J.)
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Utilizing MRI, [18F...
Utilizing MRI, [18F]FDG-PET and [89Zr]Zr-DFO-28H1 FAP-PET tracer to assess inflammation and fibrogenesis in a reproducible lung injury rat model : a multimodal imaging study
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- Boswinkel, Milou (författare)
- Radboud University Medical Center
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- Raavé, René (författare)
- Radboud University Medical Center
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- Veltien, Andor (författare)
- Radboud University Medical Center
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- Scheenen, Tom W.J. (författare)
- Radboud University Medical Center
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- Fransén Petterson, Nina (författare)
- Truly Labs
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- in ‘t Zandt, René (författare)
- Lund University,Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,MR Physics,Forskargrupper vid Lunds universitet,Faculty of Medicine,Lund University Research Groups
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- Olsson, Lars E. (författare)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,Medical Radiation Physics, Malmö,Lund University Research Groups,Skåne University Hospital
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- von Wachenfeldt, Karin (författare)
- Truly Labs
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- Heskamp, Sandra (författare)
- Radboud University Medical Center
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- Mahmutovic Persson, Irma (författare)
- Lund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,Lund University Bioimaging Center,Medicinska fakulteten,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Neurovaskulär forskning,Medical Radiation Physics, Malmö,Lund University Research Groups,Faculty of Medicine,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Applied Neurovascular Research
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Frontiers in Nuclear Medicine. - 2673-8880. ; 3
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- Objective: Accurate imaging biomarkers that indicate disease progression at an early stage are highly important to enable timely mitigation of symptoms in progressive lung disease. In this context, reproducible experimental models and readouts are key. Here, we aim to show reproducibility of a lung injury rat model, by inducing disease and assessing disease progression by multi-modal non-invasive imaging techniques at two different research sites. Furthermore, we evaluated the potential of fibroblast activating protein (FAP) as an imaging biomarker in the early stage of lung fibrosis. Methods: An initial lung injury rat model was set up at one research site (Lund University, Lund, Sweden) and repeated at a second site (Radboudumc, Nijmegen, The Netherlands). To induce lung injury, Sprague-Dawley rats received intratracheal instillation of bleomycin as one single dose (1,000 iU in 200 µL) or saline as control. Thereafter, longitudinal images were acquired to track inflammation in the lungs, at 1 and 2 weeks after the bleomycin challenge by magnetic resonance imaging (MRI) and [18F]FDG-PET. After the final [18F]FDG-PET scan, rats received an intravenous tracer [89Zr]Zr-DFO-28H1 (anti-FAP antibody) and were imaged at day 15, to track fibrogenesis. Upon termination, bronchoalveolar lavage (BAL) was performed to assess cell and protein concentration. Subsequently, the biodistribution of [89Zr]Zr-DFO-28H1 was measured ex vivo and the spatial distribution in lung tissue was studied by autoradiography. Lung sections were stained, and fibrosis assessed using the modified Ashcroft score. Results: Bleomycin-challenged rats showed body weight loss and increased numbers of immune cells and protein concentrations after BAL compared with control animals. The initiation and progression of the disease were reproduced at both research sites. Lung lesions in bleomycin-exposed rats were visualized by MRI and confirmed by histology. [18F]FDG uptake was higher in the lungs of bleomycin-challenged rats compared with the controls, similar to that observed in the Lund study. [89Zr]Zr-DFO-28H1 tracer uptake in the lung was increased in bleomycin-challenged rats compared with control rats (p = 0.03). Conclusion: Here, we demonstrate a reproducible lung injury model and monitored disease progression using conventional imaging biomarkers MRI and [18F]FDG-PET. Furthermore, we showed the first proof-of-concept of FAP imaging. This reproducible and robust animal model and imaging experimental set-up allows for future research on new therapeutics or biomarkers in lung disease.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Nyckelord
- animal models
- bleomycin
- fibroblast activating protein (FAP)
- imaging
- lung fibrosis
- magnetic resonance imaging (MRI)
- positron emission tomography (PET)
- reproducibility experiments
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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