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Abstract <p>Knowledge of tumor absorbed dose (AD)–response relationships is a critical first step toward personalizing dose regimens. This study investigated these relationships at a preclinical scale and modeled the observed tumor growth by considering both cellular AD-response relationships and tumor AD distributions. Using this framework, we compared the tumor AD-response of [<sup>177</sup>Lu]Lu-DOTATATE and [<sup>161</sup>Tb]Tb-DOTATATE.</p> Methods <p>CA20948 xenograft-bearing mice were injected with a range of activities of [<sup>177</sup>Lu]Lu-DOTATATE (1 nmol, 21.6–115.4 MBq) and [<sup>161</sup>Tb]Tb-DOTATATE (1 nmol, 17.3–91.7 MBq). The tumor doubling time was measured and correlated with individual tumor AD, determined with micro-SPECT imaging. The tumor-growth was also modeled based on cellular AD-response relationships, while considering subtumor AD distributions that were determined either with digital autoradiography or micro-SPECT.</p> Results <p>[<sup>161</sup>Tb]Tb-DOTATATE showed a 30% higher S-value for tumors compared to [<sup>177</sup>Lu]Lu-DOTATATE, after a correction for subcellular heterogeneity. Both treatments reached a clinically relevant tumor AD-range of 9–85&#xa0;Gy and 5–87&#xa0;Gy, respectively. A positive correlation was observed between the tumor doubling time and the tumor AD (p <i>&lt;</i> 0.0001, <i>R</i><sup>2</sup> = 0.58), with no significant difference in AD-response between [<sup>177</sup>Lu]Lu-DOTATATE and [<sup>161</sup>Tb]Tb-DOTATATE (<i>p</i> = 0.24). The performance of the tumor-growth-model improved substantially after considering AD heterogeneity (from <i>R</i><sup>2</sup> = -64 up to <i>R</i><sup>2</sup> = 0.16).</p> Conclusion <p>The tumor doubling time showed a positive correlation with the tumor AD which was largely affected by the heterogeneous AD distribution within the tumor. Findings confirm that [<sup>161</sup>Tb]Tb-DOTATATE does not increase the therapeutic efficacy compared to [<sup>177</sup>Lu]Lu-DOTATATE.</p>

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From uniform to heterogeneous dose models: connecting cellular and tumor absorbed dose-response for [177Lu]Lu-DOTATATE and [161Tb]Tb-DOTATATE

  • 期刊论文

  • 发表日期：

    2026年2月9日

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  • Kaat Spoormans,
  • Lara Struelens,
  • Michel Koole,
  • Melissa Crabbé

摘要

Abstract

Knowledge of tumor absorbed dose (AD)–response relationships is a critical first step toward personalizing dose regimens. This study investigated these relationships at a preclinical scale and modeled the observed tumor growth by considering both cellular AD-response relationships and tumor AD distributions. Using this framework, we compared the tumor AD-response of [177Lu]Lu-DOTATATE and [161Tb]Tb-DOTATATE.

Methods

CA20948 xenograft-bearing mice were injected with a range of activities of [177Lu]Lu-DOTATATE (1 nmol, 21.6–115.4 MBq) and [161Tb]Tb-DOTATATE (1 nmol, 17.3–91.7 MBq). The tumor doubling time was measured and correlated with individual tumor AD, determined with micro-SPECT imaging. The tumor-growth was also modeled based on cellular AD-response relationships, while considering subtumor AD distributions that were determined either with digital autoradiography or micro-SPECT.

Results

[161Tb]Tb-DOTATATE showed a 30% higher S-value for tumors compared to [177Lu]Lu-DOTATATE, after a correction for subcellular heterogeneity. Both treatments reached a clinically relevant tumor AD-range of 9–85 Gy and 5–87 Gy, respectively. A positive correlation was observed between the tumor doubling time and the tumor AD (p < 0.0001, R2 = 0.58), with no significant difference in AD-response between [177Lu]Lu-DOTATATE and [161Tb]Tb-DOTATATE (p = 0.24). The performance of the tumor-growth-model improved substantially after considering AD heterogeneity (from R2 = -64 up to R2 = 0.16).

Conclusion

The tumor doubling time showed a positive correlation with the tumor AD which was largely affected by the heterogeneous AD distribution within the tumor. Findings confirm that [161Tb]Tb-DOTATATE does not increase the therapeutic efficacy compared to [177Lu]Lu-DOTATATE.