Despite numerous clinical trials and pre-clinical developments, the treatment of glioblastoma (GB) remains a
challenge. The current survival rate of GB averages one year, even with an optimal standard of care. However,
the future promises efficient patient-tailored treatments, including targeted radionuclide therapy (TRT).
Advances in radiopharmaceutical development have unlocked the possibility to assess disease at the molecular
level allowing individual diagnosis. This leads to the possibility of choosing a tailored, targeted approach for
therapeutic modalities. Therapeutic modalities based on radiopharmaceuticals are an exciting development
with great potential to promote a personalised approach to medicine. However, an effective targeted
radionuclide therapy (TRT) for the treatment of GB entails caveats and requisites. This review provides an
overview of existing nuclear imaging and TRT strategies for GB. A critical discussion of the optimal
characteristics for new GB targeting therapeutic radiopharmaceuticals and clinical indications are provided.
Considerations for target selection are discussed, i.e. specific presence of the target, expression level and
pharmacological access to the target, with particular attention to blood-brain barrier crossing. An overview of
the most promising radionuclides is given along with a validation of the relevant radiopharmaceuticals and
theranostic agents (based on small molecules, peptides and monoclonal antibodies). Moreover, toxicity issues
and safety pharmacology aspects will be presented, both in general and for the brain in particular.http://www.thno.orgdm2022Nuclear Medicin