Abrantes A M, Serra E, Goncalves C, Oliveiros B, Laranjo M, Sarmento-Ribeiro A B, Rocha-Gonsalves A, Botelho M F
Biophysics/Biomatematics Institute, IBILI, Faculty of Medicine, University of Coimbra, Portugal.
Curr Radiopharm. 2012 Apr;5(2):99-105. doi: 10.2174/1874471011205020099.
Hypoxia is a biochemical condition where reduced oxygen partial pressure at tissue level occurs. This metabolic situation can lead to resistance to radio and chemotherapy. In malignant solid tumours, hypoxia is a common characteristic, having a great impact at biological level, being of tremendous importance for complete understanding of tumour progression.
We studied the behavior of 99mTc-HL91 in vivo, using an animal model based on Balb-c nu/nu mice with a xenotransplant of the human colorectal adenocarcinoma cell line, WiDr.
In vivo studies using an animal model of xenograft on Balb/c nu/nu nude mice were carried out. This model, allowed us to evaluate the radiopharmaceutical biodistribution and to calculate tumour/muscle ratio, acquired after 99mTc-HL91 injection. We also performed ex vivo studies, using the excised tumours to access viability and to characterize the intracellular production of reactive oxygen species and the status of mitochondrial membrane potential through flow cytometry.
The biodistribution after 99mTc-HL91 injection showed urinary and hepatobilliary excretion in similar proportions and tumour uptake around 4.4% of administered activity. This uptake was higher at the bigger tumours. Through flow cytometry we observed that larger tumours have a higher amount of reactive oxygen species and a decrease in mitochondrial membrane potential.
99mTc-HL91 allowed a non-invasive evaluation of the solid tumours oxidative state by nuclear medicine functional imaging. This information can be of high importance at the pre-treatment estimation of this type of tumours.
缺氧是一种在组织水平上氧分压降低的生化状态。这种代谢情况可导致对放疗和化疗产生抗性。在恶性实体瘤中，缺氧是一个常见特征，在生物学层面有重大影响，对于全面理解肿瘤进展极为重要。
我们使用基于Balb-c nu/nu小鼠的动物模型，该模型移植了人结肠直肠腺癌细胞系WiDr，研究了99mTc-HL91在体内的行为。
在Balb/c nu/nu裸鼠异种移植动物模型上进行了体内研究。该模型使我们能够评估放射性药物的生物分布，并计算99mTc-HL91注射后获得的肿瘤/肌肉比值。我们还进行了体外研究，使用切除的肿瘤通过流式细胞术评估活力、表征细胞内活性氧的产生以及线粒体膜电位状态。
99mTc-HL91注射后的生物分布显示，尿液和肝胆排泄比例相似，肿瘤摄取约为给药活性的4.4%。在较大肿瘤中这种摄取更高。通过流式细胞术我们观察到，较大肿瘤具有更高量的活性氧且线粒体膜电位降低。
99mTc-HL91通过核医学功能成像实现了对实体瘤氧化状态的无创评估。该信息在这类肿瘤的治疗前评估中可能非常重要。
