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Cleaved CD31 as a target for in vivo molecular imaging of inflammation
Jonathan Vigne1,2,3, Sylvie Bay4,5, Rachida Aid-Launais6,7
1Nuclear Medicine Department, X. Bichat Hospital, APHP and DHU FIRE, F-75018, Paris, France. jonathan.vigne.fr@gmail.com.
Abstract:
There is a need for new targets to specifically localize inflammatory foci, usable in a wide range of organs. Here, we hypothesized that the cleaved molecular form of CD31 is a suitable target for molecular imaging of inflammation. We evaluated a bioconjugate of D-P8RI, a synthetic peptide that binds all cells with cleaved CD31, in an experimental rat model of sterile acute inflammation. Male Wistar rats were injected with turpentine oil into the gastrocnemius muscle two days before 99mTc-HYNIC-D-P8RI (or its analogue with L-Proline) SPECT/CT or [18F]FDG PET/MRI. Biodistribution, stability study, histology, imaging and autoradiography of 99mTc-HYNIC-D-P8RI were further performed. Biodistribution studies revealed rapid elimination of 99mTc-HYNIC-D-P8RI through renal excretion with almost no uptake from most organs and excellent in vitro and in vivo stability were observed. SPECT/CT imaging showed a significant higher 99mTc-HYNIC-D-P8RI uptake compared with its analogue with L-Proline (negative control) and no significant difference compared with [18F]FDG (positive control). Moreover, autoradiography and histology revealed a co-localization between 99mTc-HYNIC-D-P8RI uptake and inflammatory cell infiltration. 99mTc-HYNIC-D-P8RI constitutes a new tool for the detection and localization of inflammatory sites. Our work suggests that targeting cleaved CD31 is an attractive strategy for the specific in vivo imaging of inflammatory processes.
Insights
Researchers developed a new molecular imaging agent targeting cleaved CD31 to detect inflammation. This agent, 99mTc-HYNIC-D-P8RI, showed high specificity and stability in preclinical models, offering a promising tool for diagnosing inflammatory diseases.
Area of Science:
- Biomedical imaging
- Molecular biology
- Radiochemistry
Background:
- Current methods for localizing inflammation lack specificity across various organs.
- Identifying novel molecular targets for imaging inflammation is crucial for early diagnosis and treatment monitoring.
- Cleaved CD31 has emerged as a potential biomarker for inflammatory processes.
Purpose of the Study:
- To evaluate the utility of a synthetic peptide bioconjugate, D-P8RI, targeting cleaved CD31 for molecular imaging of inflammation.
- To assess the biodistribution, stability, and imaging capabilities of 99mTc-HYNIC-D-P8RI in a rat model of sterile acute inflammation.
Main Methods:
- A rat model of turpentine-induced sterile acute inflammation was established.
- 99mTc-HYNIC-D-P8RI and a control analogue were administered and imaged using SPECT/CT.
- [18F]FDG PET/MRI was used for comparison.
- Biodistribution, stability studies, histology, and autoradiography were performed.
Main Results:
- 99mTc-HYNIC-D-P8RI demonstrated rapid renal excretion and high in vitro/in vivo stability.
- SPECT/CT imaging revealed significantly higher uptake of 99mTc-HYNIC-D-P8RI compared to the control and comparable uptake to [18F]FDG.
- Autoradiography and histology confirmed co-localization of the tracer with inflammatory cell infiltration.
Conclusions:
- Targeting cleaved CD31 with 99mTc-HYNIC-D-P8RI is a viable strategy for specific in vivo imaging of inflammatory foci.
- This novel agent offers a promising new tool for the detection and localization of inflammatory sites across multiple organs.
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