Purpose

¹⁷⁷Lu-OncoFAP-23 is a novel FAP-targeted radioligand therapeutic (RLT) with high and prolonged tumor residence time and promising preclinical efficacy. In this work, we investigated the correlation between the injected molar dose and the in vivo tumor-to-organ ratios and tumor-targeting performance of ¹⁷⁷Lu-OncoFAP-23.

Methods

We evaluated the quantitative biodistribution profile of ¹⁷⁷Lu-OncoFAP-23 at different molar doses (i.e., 3 to 2250 nmol/kg) in tumor-bearing mice by means of ex vivo gamma counting, we included ¹⁷⁷Lu-OncoFAP and ¹⁷⁷Lu-BiOncoFAP as experimental controls.

Results

The biodistribution profile of ¹⁷⁷Lu-OncoFAP-23 strongly depends on the molar dose injected. Molar doses below 30 nmol/kg result in unwanted uptake of the compound in healthy organs, while doses higher than 725 nmol/kg determined a reduced tumor uptake due to receptor saturation. We identified an optimal molar dose ranging from 90 to 250 nmol/kg, characterized by elevated tumor uptake and adequate tumor-to-organ ratios.

Conclusion

¹⁷⁷Lu-OncoFAP-23 presents a favorable in vivo biodistribution profile at molar doses ranging from 90 to 250 nmol/kg in tumor-bearing mice. Our results guide the design of the first-in-human Phase I clinical trial with this novel FAP-targeted radioligand therapeutic.

Graphical abstract

中文翻译：

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摩尔剂量对 FAP 靶向放射性配体治疗药物体内组织生物分布谱的影响

 目的

¹⁷⁷ 元Lu-OncoFAP-23 是一种新型的 FAP 靶向放射配体治疗药物 （RLT），具有较长且较长的肿瘤停留时间和良好的临床前疗效。在这项工作中，我们研究了注射的摩尔剂量与 ¹⁷⁷个 Lu-OncoFAP-23 的体内肿瘤器官比和肿瘤靶向性能之间的相关性。

 方法

我们通过离体 γ 计数评估了不同摩尔剂量 （即 3 至 2250 nmol/kg） 的 ¹⁷⁷Lu-OncoFAP-23 在荷瘤小鼠中的定量生物分布曲线，我们包括 ¹⁷⁷个 Lu-OncoFAP 和 ¹⁷⁷个 Lu-BiOncoFAP 作为实验对照。

 结果

¹⁷⁷Lu-OncoFAP-23 的生物分布特征强烈取决于注射的摩尔剂量。低于 30 nmol/kg 的摩尔剂量导致健康器官对化合物的不必要摄取，而高于 725 nmol/kg 的剂量决定了由于受体饱和而导致的肿瘤摄取减少。我们确定了 90 至 250 nmol/kg 的最佳摩尔剂量，其特征是肿瘤摄取升高和足够的肿瘤器官比。

 结论

¹⁷⁷ 元Lu-OncoFAP-23 在荷瘤小鼠中以 90 至 250 nmol/kg 的摩尔剂量呈现良好的体内生物分布曲线。我们的结果指导了这种新型 FAP 靶向放射配体治疗药物的首次人体 I 期临床试验的设计。

 图形摘要