Table 1. Pathway to implementing GNPs as clinical agents.

Stage	Aims
Tumor site identification	Identify a tumor site, which may benefit significantly from introduction of GNP contrast agents (see table 2).
GNP design	Design a GNP to efficiently target tumor site, optimizing particle size and functionalization based on tumor characteristics (table 3).
in vitro validation	in vitro models can be used to confirm basic biocompatibility of GNP preparation and radiosensitizing properties (table 4).
in vivo validation	Validated GNP preparations should undergo in vivo validation in preclinical models. This should include both, toxicity testing in relevant animal models, as well as validation of radiosensitizing effects in models recapitulating relevant tumor biology (table 4).
Physics validation	Physics models must be tested and updated as necessary to enable accurate planning and dosimetry in situations where GNPs introduce significant concentrations of high-Z materials within treatment fields.
Clinical validation	Following comprehensive pre-clinical validation, GNPs must be validated through the established clinical trial pathway, ensuring acceptable toxicity, compatibility with existing chemotherapeutic regimes and radiobiological effectiveness (table 5).