Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN, USA.
Department of Physics and Astronomy, College of Science, Purdue University, West Lafayette, IN, USA.
Vet Med Sci. 2021 May;7(3):665-673. doi: 10.1002/vms3.423. Epub 2020 Dec 24.
Neutropenia is the most common dose-limiting side effect of cytotoxic chemotherapy in cancer-bearing dogs. Biodynamic imaging (BDI) is a functional imaging technology that measures dynamic light scattering from living, three-dimensional tissues to characterize intracellular motion within those tissues. Previous studies have associated BDI biomarkers with tumour sensitivity to chemotherapy agents in dogs with naturally occurring cancer. We hypothesized that BDI, performed ex vivo on bone marrow aspirate samples, would identify dynamic biomarkers associated with the occurrence of specific degrees of neutropenia in tumour-bearing dogs receiving doxorubicin chemotherapy.
Bone marrow aspirates were collected from 10 dogs with naturally occurring cancers prior to initiation of doxorubicin treatment. BDI was performed on bone marrow samples treated ex vivo with doxorubicin at 0.1, 1, 10 and 100 μM along with 0.1% DMSO as a control. Dogs then were treated with doxorubicin (30 mg/m , intravenously). Peripheral blood neutrophil counts were obtained on the day of treatment and again 7 days later. Receiver operating characteristic curves identified provisional breakpoints for BDI biomarkers that correlated with specific changes in neutrophil counts between the two time points.
Provisional breakpoints for several BDI biomarkers were identified, specifying dogs with the largest proportionate change in neutrophils and with neutropenia that was grade 2 or higher following doxorubicin treatment.
Biodynamic imaging of bone marrow aspirates may identify those dogs at greater risk for neutropenia following doxorubicin chemotherapy. This approach may be useful for pre-emptively modifying chemotherapy dosing in dogs to avoid unacceptable side effects.
中性粒细胞减少是荷瘤犬接受细胞毒性化疗最常见的剂量限制副作用。生物动力学成像（BDI）是一种功能成像技术，可测量来自三维活组织的动态光散射，以表征组织内的细胞内运动。先前的研究将 BDI 生物标志物与狗自然发生癌症中对化疗药物的肿瘤敏感性相关联。我们假设，在接受阿霉素化疗的荷瘤犬中，对骨髓抽吸样本进行离体 BDI 将识别出与特定程度中性粒细胞减少发生相关的动态生物标志物。
在开始阿霉素治疗前，从 10 只患有自然发生癌症的犬中收集骨髓抽吸物。对离体用阿霉素（0.1、1、10 和 100 μM）和 0.1% DMSO （作为对照）处理的骨髓样本进行 BDI。然后，犬接受阿霉素（30 mg/m ，静脉内）治疗。在治疗当天和 7 天后获取外周血中性粒细胞计数。接受者操作特征曲线确定与两次时间点之间中性粒细胞计数特定变化相关的 BDI 生物标志物的暂定临界点。
确定了几个 BDI 生物标志物的暂定临界点，指定了在阿霉素治疗后中性粒细胞比例变化最大且中性粒细胞减少为 2 级或更高的犬。
骨髓抽吸物的生物动力学成像可能会识别出那些在接受阿霉素化疗后更容易发生中性粒细胞减少的犬。这种方法可能有助于预先调整犬的化疗剂量，以避免不可接受的副作用。
