Macrophage mannose receptor CD206 targeting of fluoride-18 labeled mannosylated dextran: A validation study in mice
In this study by Andriana et al., PET/CT imaging using the β-CUBE (PET) and X-CUBE (CT) demonstrates that the novel radiotracer Al[18F]F-NOTA-D10CM effectively targets the CD206 receptor for inflammation imaging.
Research question
The macrophage mannose receptor (CD206) is a 175 kDa C-type lectin transmembrane protein involved in immune signaling during inflammation. It’s found in lymph nodes and lymphatic vessels, making it a promising target for imaging inflammation. Molecular imaging of CD206 could help track disease activity and treatment response.
In this study, a novel PET radiotracer, Al[18F]F-NOTA-D10CM, targeting CD206 was investigated.
The ability to target the CD206 was validated by comparing the tracer’s distribution in CD206 knockout (CD206 KO) and wild-type (WT) mice, and its uptake was studied in inflamed tissues and lymph nodes in a mouse model of complete Freund’s adjuvant (CFA)-induced inflammation.
Experiment
Mice were imaged with PET/CT under isoflurane anesthesia and on consecutive days. A 20-minute static PET acquisition was performed 90 minutes post-injection of [18F]FDG (4.95 ± 0.51 MBq). With Al[18F]F-NOTA-D10CM (5.66 ± 2.18 MBq intravenous and 4.55 ± 1.69 MBq intradermal into the left hind paw), a 120-minute dynamic PET acquisition was started.
On the last day of the study, the mice were intravenously injected with Al[18F]F-NOTA-D10CM (7.55 ± 2.84 MBq) and ex vivo analyses were performed 60 min post-injection.
CT was performed for attenuation correction and anatomical reference. PET/CT images were analyzed using Carimas 2.10 software.
Results
The uptake of Al[18F]F-NOTA-D10CM was significantly lower in CD206 KO compared to WT mice. Experiments in mice with CFA-induced inflammation and healthy controls showed that the uptake of Al[18F]F-NOTA-D10CM was significantly higher in inflamed ankle joint and foot pad skin in contrast to the tissue in heathy mice.
Intravenous and intradermal tracer administration was compared for inflammation imaging, with the intradermal route showing more specificity for visualizing lymphatics and lymph node activation.
In conclusion, the results indicate that Al[18F]F-NOTA-D10CM specifically detects CD206 in inflamed tissue, resulting in a promising tracer for inflammation imaging.
Figure adapted from Andriana, Putri, et al. European Journal of Nuclear Medicine and Molecular Imaging 51.8 (2024): 2216-2228.
A: In vivo PET/CT after intradermal injection of Al[18F] F-NOTA-D10CM (white arrows) reveals a change in the lymphatic drainage pathway after induction of inflammation by complete Freund’s adjuvant (CFA).
B: In healthy mice, the tracer was distributed from the popliteal to the iliac and renal lymph nodes, with minimal uptake in the inguinal node. After CFA induction, tracer uptake shifted progressively toward the inguinal lymph node, showing a significant increase by day 14 (P = 0.002).
