Challenges in tracer development for tumor microenvironment (TME) imaging.

However, since the intended application of immune-cell targeted tracers is the in vivo imaging of immune cells and their dynamic tissue distribution over time (not a bulk of target-positive tumor cells), there is an increasing trend towards using more sophisticated models such as hCD4-knock in (replacement of mouse protein by human protein) [ 47 , 188 ] or hCD8 transgenic models (co-expression of hCD8 with endogenous mCD8) [ 42 ] to additionally corroborate the target specificity of the tracer and its capacity to detect the inherently low endogenous target expression in the immune system.

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