Clinical Trials in Molecular Radiotherapy: An Overview of the Landscape

In recent years the treatment of cancer with radioactive drugs, here termed molecular radiotherapy (MRT), has emerged to take a place alongside other treatment modalities, particularly non-radioactive drugs (NRDs) and external beam radiotherapy (EBRT). A purpose-built tool was developed within the Python programming environment to review the evolution of clinical trials performed in the first quarter of the century as recorded by the ClinicalTrials.gov database. It was found that the number of MRT trials registered on ClinicalTrials.gov increased by 15-fold from 6 trials in 2000 to 89 in 2024. The ratio of MRT clinical trials relative to EBRT has remained constant at approximately 1:5. Although the number of MRT trials has remained comparatively low, their frequency in relation to NRD trials has doubled over the 25-year period. All modalities have been investigated in a similar spread of early and late phase trials, with a slightly higher proportion for early phase trials in MRT. The registration of trials has increased for almost all indications, particularly for prostate, neuroendocrine and liver cancers, although the number of trials for lymphoma has declined. The diversity and number of radionuclides involved in MRT clinical trials have increased, with beta-minus emitting radionuclides accounting in 2024 for approximately 89% of studies compared to 11% for alpha-emitters.