目的:由于急性髓性白血病仍然是成人急性白血病中最具侵袭性的类型,对疾病病理学的深刻理解对于诊断和治疗目的至关重要。因此,本研究旨在通过临床前正电子发射断层扫描(PET)和全身放射自显影建立实验性骨髓母细胞白血病(My1/De)大鼠模型,探讨实时疾病命运。
方法:进行了体外[18F]F-FDG摄取研究,以比较新培养的My1/De肿瘤细胞系(母细胞)与健康对照和My1/De骨髓悬浮液中的示踪剂积累。Long-Evans大鼠左肾包膜下My1/De细胞移植后,原发性My1/肿瘤发生,使用[18F]F-FDGPET成像研究转移传播,全身放射自显影和磷酸化图像分析。为了评估携带肿瘤的动物的器官摄取概况,我们完成了离体生物分布研究。
结果:My1/De培养细胞中的示踪剂积累超过了肿瘤和健康骨髓悬浮液(p<0.01)。基于体内成像,肾下移植的My1/De细胞导致腹部器官白血病的发展,并转移到肠系膜和胸膜旁淋巴结(PTLN)。转移性PTLN的%ID/g值(4.25±0.28)与对照(0.94±0.34)相比显著更高,进一步证实了转移的淋巴扩散。外周血的细胞化学染色,尸检结果,wright-Giemsa染色的死后组织学切片证明了评估组织/器官的白血病参与。
结论:目前建立的My1/De模型似乎非常适合于进一步的白血病相关治疗和诊断研究。
OBJECTIVE: Since acute myeloid leukemias still represent the most aggressive type of adult acute leukemias, the profound understanding of disease pathology is of paramount importance for diagnostic and therapeutic purposes. Hence, this study aimed to explore the real-time disease fate with the establishment of an experimental myelomonoblastic leukemia (My1/De) rat model using preclinical positron emission tomography (PET) and whole-body
autoradiography.
METHODS: In vitro [18F]F-FDG uptake studies were performed to compare the tracer accumulation in the newly cultured My1/De tumor cell line (blasts) with that in healthy control and My1/De bone marrow suspensions. Post transplantation of My1/De cells under the left renal capsule of Long-Evans rats, primary My1/De tumorigenesis, and metastatic propagation were investigated using [18F]F-FDG PET imaging, whole-body
autoradiography and phosphorimage analyses. To assess the organ uptake profile of the tumor-carrying animals we accomplished ex vivo biodistribution studies.
RESULTS: The tracer accumulation in the My1/De culture cells exceeded that of both the tumorous and the healthy bone marrow suspensions (p<0.01). Based on in vivo imaging, the subrenally transplanted My1/De cells resulted in the development of leukemia in the abdominal organs, and metastasized to the mesenterial and thoracic parathymic lymph nodes (PTLNs). The lymphatic spread of metastasis was further confirmed by the significantly higher %ID/g values of the metastatic PTLNs (4.25±0.28) compared to the control (0.94±0.34). Cytochemical staining of the peripheral blood, autopsy findings, and wright-Giemsa-stained post-mortem histological sections proved the leukemic involvement of the assessed tissues/organs.
CONCLUSIONS: The currently established My1/De model appears to be well-suited for further leukemia-related therapeutic and diagnostic investigations.