Imaging Immune Response with sdAbs

The interplay between stromal cells, tumor cells, and migratory cells such as lymphocytes creates opportunities for noninvasive imaging of immune responses. Experienced in single domain antibody (sdAb) development and antibody site-specific conjugation, Creative Biolabs offers various labeling approaches to develop sdAb-based imaging tracers. In vivo imaging services will be tailored according to your specific project demands. By using a combination of sdAb, we will choose the best one to track immune responses with excellent specificity.

Significance of Imaging Immune Response

Tumors are often surrounded and invaded by bone marrow-derived cells. Imaging the infiltration of such immune cells into tumors provides an attractive means of detecting tumors or of tracking the response to anticancer therapy. Reports show that it is possible to detect these cells non-invasively by various techniques such as positron emission tomography (PET) via the surface markers displayed by them. The ability to monitor the immune response in the course of therapy will enable early determination of the efficacy of treatment and will inform decisions as to whether treatment should be stopped or continued. Noninvasive monitoring could thus change how therapies are applied and assessed.

Imaging Examples

Radiolabeled anti-murine class II major histocompatibility complex (MHC II) and CD11b sdAbs were developed to assess immune infiltrates in different tumor models. The radiolabeled anti-class II MHC and anti-CD11b sdAbs were then used to detect tumors in both xenogeneic and syngeneic tumor models. Similarly, to image human immune responses, an anti-human MHC IIb sdAb was developed and the radiolabeled sdAb was used in a relevant humanized mouse model to detected graft-versus-host disease. In diseased animals, a significant increase in PET signal in the liver was detected, which was attributed to the infiltration of activated class II MHC⁺ T cells. The method may thus be more generally useful to diagnose inflammation.

Cytotoxic CD8⁺ T cells mediate much of the response to checkpoint blockade. Monitoring the distribution of CD8⁺ T cells could be used to assess the response to therapy. A ⁸⁹Zr-labeled anti-CD8 sdAb was used to perform PET on mice. PET images showed label accumulation in lymphoid organs, as well as in the kidneys and bladder. The addition of a PEG molecule was found to improve the efficiency of staining and decrease non-specific uptake in the kidneys.

Fig.1 PEGylation increases sensitivity and decreases kidney retention of radiolabeled sdAb. (Rashidian, 2015)

Common Tools

Customized Services

• Generation and in vitro characterization of sdAb
• Tailored PEG modification for lead sdAb
• Nanotracers construction services
• In vitro assessment services
• In vivo imaging services
• Statistical analysis

With the availability of anti-human sdAb, the ability to monitor the presence or absence of neutrophils and activated macrophages as an indicator of inflammation should be transposable to a pre-clinical or clinical setting as a diagnostic tool. Creative Biolabs customized imaging sdAb-based tracer development services for global clients. If you are interested in our services, please feel free to contact us for more information.

Reference

1. Rashidian, M.; et al. Noninvasive imaging of immune responses. Proceedings of the National Academy of Sciences. 2015, 112(19): 6146-6151.

For Research Use Only.