Purpose

This study by the EANM radiobiology working group aims to analyze the efficacy and toxicity of targeted radionuclide therapy (TRT) using radiopharmaceuticals approved by the EMA and FDA for neuroendocrine tumors and prostate cancer. It seeks to understand the correlation between physical parameters such as absorbed dose and TRT outcomes, alongside other biological factors.

Methods

We reviewed clinical studies on TRT, focusing on the relationship between physical parameters and treatment outcomes, and applying basic radiobiological principles to radiopharmaceutical therapy to identify key factors affecting therapeutic success.

Results

The analysis revealed that mean absorbed dose alone is insufficient to predict treatment response or toxicity. For absorbed doses below a certain threshold, outcomes are unpredictable, while doses above this threshold improve the likelihood of biological responses. However, even at higher absorbed doses, response plateaus indicate the need for additional parameters to explain outcome variability, including heterogeneity in target expression, anatomical disease location, (epi)genetics, DNA repair capacity, and the tumor microenvironment, aspects that will be discussed in Part II of this analysis.

Conclusion

Understanding radiobiology is crucial for optimizing TRT. More dosimetric data is needed to refine treatment protocols. While absorbed dose is critical, it alone does not determine TRT outcomes. Future research should integrate biological parameters with physical dosimetry to enhance efficacy and minimize toxicity.

中文翻译：

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EANM 专家意见：如何将放射生物学的经验教训应用于临床试验的设计？第一部分：回到吸收剂量-反应和阈值吸收剂量的基础知识

 目的

EANM 放射生物学工作组的这项研究旨在分析使用 EMA 和 FDA 批准的放射性药物治疗神经内分泌肿瘤和前列腺癌的靶向放射性核素治疗 （TRT） 的疗效和毒性。它试图了解吸收剂量和 TRT 结果等物理参数以及其他生物因素之间的相关性。

 方法

我们回顾了 TRT 的临床研究，重点关注物理参数与治疗结果之间的关系，并将基本放射生物学原理应用于放射药物治疗，以确定影响治疗成功的关键因素。

 结果

分析显示，仅平均吸收剂量不足以预测治疗反应或毒性。对于低于某个阈值的吸收剂量，结果是不可预测的，而高于该阈值的剂量会提高生物反应的可能性。然而，即使在较高的吸收剂量下，反应平台期也表明需要额外的参数来解释结果变异性，包括靶点表达的异质性、解剖疾病位置、（表观）遗传学、DNA 修复能力和肿瘤微环境，这些方面将在本分析的第二部分中讨论。

 结论

了解放射生物学对于优化 TRT 至关重要。需要更多的剂量学数据来完善治疗方案。虽然吸收剂量至关重要，但它本身并不能决定 TRT 结果。未来的研究应将生物参数与物理剂量学相结合，以提高疗效并最大限度地减少毒性。