使用 MIRDcell V3 预测微转移灶的反应：用 Ac-DOTA 包封脂质体在肿瘤球体中产生不同的活性分布来证明原理。
Predicting response of micrometastases with MIRDcell V3: proof of principle with Ac-DOTA encapsulating liposomes that produce different activity distributions in tumor spheroids.
机构信息
Division of Radiation Research, Department of Radiology and Center for Cell Signaling, New Jersey Medical School, Rutgers University, 205 S. Orange Avenue, Newark, NJ, 07103, USA.
Department of Chemical and Biomolecular Engineering, Institute for NanoBioTechnology, Johns Hopkins University, Baltimore, MD, USA.
出版信息
Eur J Nucl Med Mol Imaging. 2022 Oct;49(12):3989-3999. doi: 10.1007/s00259-022-05878-7. Epub 2022 Jul 8.
PURPOSE
The spatial distribution of radiopharmaceuticals within multicellular clusters is known to have a significant effect on their biological response. Most therapeutic radiopharmaceuticals distribute nonuniformly in tissues which makes predicting responses of micrometastases challenging. The work presented here analyzes published temporally dependent nonuniform activity distributions within tumor spheroids treated with actinium-225-DOTA encapsulating liposomes (Ac-liposomes) and uses these data in MIRDcell V3.11 to calculate absorbed dose distributions and predict biological response. The predicted responses are compared with experimental responses.
METHODS
Four types of liposomes were prepared having membranes with different combinations of release (R) and adhesion (A) properties. The combinations were RA, RA, RA, and RA. These afford different penetrating properties into tissue. The liposomes were loaded with either carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) or Ac. MDA-MB-231 spheroids were treated with the CFDA-SE-liposomes, harvested at different times, and the time-integrated CFDA-SE concentration at each radial position within the spheroid was determined. This was translated into mean Ac decays/cell versus radial position, uploaded to MIRDcell, and the surviving fraction of cells in spherical multicellular clusters was simulated. The MIRDcell-predicted surviving fractions were compared with experimental fractional-outgrowths of the spheroids following treatment with Ac-liposomes.
RESULTS
The biological responses of the multicellular clusters treated with Ac-liposomes with physicochemical properties RA, RA, and RA were predicted by MIRDcell with statistically significant accuracy. The prediction for RA was not predicted accurately.
CONCLUSION
In most instances, MIRDcell predicts responses of spheroids treated with Ac-liposomes that result in different tissue-penetrating profiles of the delivered radionuclides.
目的
放射性药物在多细胞簇中的空间分布对其生物学反应有显著影响。大多数治疗放射性药物在组织中分布不均匀，这使得预测微转移灶的反应具有挑战性。本文分析了已发表的关于用钍-225-DOTA 包封脂质体（Ac-脂质体）处理肿瘤球体时随时间变化的非均匀活性分布，并在 MIRDcell V3.11 中使用这些数据计算吸收剂量分布并预测生物学反应。预测的反应与实验反应进行了比较。
方法
制备了四种具有不同释放（R）和粘附（A）特性组合的脂质体。这些组合是 RA、RA、RA 和 RA。这些脂质体具有不同的穿透组织的特性。脂质体装载了羧基荧光素二乙酸琥珀酰亚胺酯（CFDA-SE）或 Ac。MDA-MB-231 球体用 CFDA-SE-脂质体处理，在不同时间收获，并确定球体每个径向位置的时间积分 CFDA-SE 浓度。这被转化为每个球体中每个径向位置的平均 Ac 衰变/细胞，并上传到 MIRDcell，模拟球形多细胞簇中细胞的存活分数。MIRDcell 预测的存活分数与用 Ac-脂质体处理后球体的实验性生长分数进行了比较。
结果
用具有 RA、RA 和 RA 理化特性的 Ac-脂质体处理的多细胞簇的生物学反应被 MIRDcell 以具有统计学意义的准确性预测。RA 的预测不准确。
结论
在大多数情况下，MIRDcell 预测了用 Ac-脂质体处理的球体的反应，导致放射性核素的不同组织穿透分布。
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