Evaluating the Immune Response After Targeted Radionuclide Therapy: Toward a Correlation Between Absorbed Dose and Response

Purpose: 

Targeted radionuclide therapy (TRT) has shown clinical successes in the treatment of neuroendocrine and prostate cancers, but curative outcomes remain limited. The immunogenic potential of TRT, particularly its ability to synergize with immunotherapies, is underexplored compared with external beam radiation therapy. This study aims to evaluate the immunogenicity of TRT by reviewing available literature and assessing the relationship between absorbed dose, dose rate, and immune response. 

Methods and Materials: 

We conducted a literature review reporting the immune response after TRT. To compare the large variety of TRT strategies used, the absorbed dose and dose rate were calculated both for the tumor site in vivo and for cultured cells in vitro. Additionally, 3 different approaches for absorbed dose calculation were assessed in vivo. Next, the correlation between these dosimetric parameters and the changes in various immune parameters between the control and TRT conditions was evaluated. 

Results: 

Twenty-four studies were included; the absorbed dose and maximum dose rate were calculated based on the initial tumor volume for all in vivo studies. A strong and statistically significant correlation was observed between the absorbed dose from TRT for CD8+ T cell activation. A nonsignificant dose-dependent association was observed for the maximum dose rate in relation to certain immune parameters, such as dendritic cell and macrophage infiltration, suggesting precise dosimetry and dose delivery kinetics are important when trying to predict TRT-induced immunogenicity. 

Conclusion: 

Current data demonstrate the immunogenic potential of TRT; however, further investigation is needed to determine the specific absorbed dose or dose rate required to modulate the immune microenvironment effectively. This knowledge is crucial to advance combination therapies with immunotherapy and TRT.