Compared to external beam radiotherapy, targeted radionuclide therapy (TRT) allows for systemic radiation treatment of metastatic lesions. Published work on recent strategies to improve patient management and response to TRT through individualising patient treatment, modifying treatment pharmacokinetics and increasing anticancer potency are discussed in this review, with a special focus on the application of clinically evaluated radiolabelled ligands and peptides in the treatment of neuroendocrine and prostate cancers.

The spatial distribution of radiopharmaceuticals that emit short-range high linear-energy-transfer electrons greatly affects the absorbed dose and their biological effectiveness. The purpose of this study was to investigate the effect of heterogeneous radionuclide distribution on tumor control probability (TCP) in a micrometastases model. were generated using an iterative modelling method based on Monte Carlo determined absorbed dose with the PENELOPE code and were compared to SFexp. Radiobiological parameters deduced from experimental results and MC simulations were used to predict the TCP for a 3-D spheroid model. Methods Results:Calculated SFs were in good agreement with experimental data, particularly when an increased value for relative biological effectiveness (RBE) was applied to self-dose deposited by sources located in the nucleus and when radiobiological parameters were adjusted to account for dose protraction. Only in MDA-MB-468 spheroids treated with 111In-EGF was a TCP>0.5 achieved, indicating that for this cell type the radiopeptide would be curative when targeting micrometastases. This is attributed to the relative radiosensitivity of MDA-MB-468 cells, high nuclear uptake of the radiopeptide and uniform distribution of radioactivity throughout the spheroid. Conclusions:It is imperative to include biological endpoints when evaluating the distribution of radionuclides in models emulating micrometastatic disease. The spatial distribution of radioactivity is a clear determinant of biological effect and TCP as demonstrated in this study.

PurposeTo assess the efficacy of different schedules for combining external beam radiotherapy (EBRT) with molecular radiotherapy (MRT) using 131I-mIBG in the management of neuroblastoma.Materials and methodsBALB/c nu/nu mice bearing SK-N-SH neuroblastoma xenografts were assigned to five treatment groups: 131I-mIBG 24 h after EBRT, EBRT 6 days after 131I-mIBG, EBRT alone, 131I-mIBG alone and control (untreated). A total of 56 mice were assigned to 3 studies. Study 1: Vessel permeability was evaluated using dynamic contrast-enhanced (DCE)-MRI (n = 3). Study 2: Tumour uptake of 131I-mIBG in excised lesions was evaluated by γ-counting and autoradiography (n = 28). Study 3: Tumour volume was assessed by longitudinal MR imaging and survival was analysed (n = 25). Tumour dosimetry was performed using Monte Carlo simulations of absorbed fractions with the radiation transport code PENELOPE.ResultsGiven alone, both 131I-mIBG and EBRT resulted in a seven-day delay in tumour regrowth. Following EBRT, vessel permeability was evaluated by DCE-MRI and showed an increase at 24 h post irradiation that correlated with an increase in 131I-mIBG tumour uptake, absorbed dose and overall survival in the case of combined treatment. Similarly, EBRT administered seven days after MRT to coincide with tumour regrowth, significantly decreased the tumour volume and increased overall survival.ConclusionsThis study demonstrates that combining EBRT and MRT has an enhanced therapeutic effect and emphasizes the importance of treatment scheduling according to pathophysiological criteria such as tumour vessel permeability and tumour growth kinetics.