After a radiopharmaceutical is administered, it distributes throughout the body according to its biological behaviour. Some tissues accumulate higher concentrations of tracer because of increased metabolism, receptor expression, perfusion, or trapping mechanisms. Other tissues show lower uptake because they lack these properties or clear the tracer more rapidly.

What determines whether a lesion is visible is not simply how much tracer it accumulates in absolute terms, but how much more it accumulates relative to surrounding tissue.

If both the lesion and background tissue have similar tracer concentrations, the lesion will blend into its surroundings. Even high absolute uptake may not be conspicuous if background activity is equally high. Conversely, a modest increase in uptake can be highly visible if background activity is low.

Target-to-background ratio therefore depends on two simultaneous processes: tracer retention within the target and tracer clearance from non-target tissues. Imaging is often timed to exploit this difference. For example, delayed imaging may improve lesion conspicuity because background activity falls while target uptake persists.

Physical factors such as scatter, attenuation, spatial resolution, and reconstruction algorithms also influence measured contrast, but the biological distribution of tracer remains the primary driver.

In quantitative imaging, TBR can be expressed as a ratio of activity concentrations (for example using SUV in PET), but conceptually it reflects relative tracer contrast.