Banzato Alessandra, Rondina Maria, Meléndez-Alafort Laura, Zangoni Elena, Nadali Anna, Renier Davide, Moschini Giuliano, Mazzi Ulderico, Zanovello Paola, Rosato Antonio
Department of Oncology and Surgical Sciences, University of Padua, Padova, Italy.
Nucl Med Biol. 2009 Jul;36(5):525-33. doi: 10.1016/j.nucmedbio.2009.02.005. Epub 2009 May 8.
Gamma-ray detectors represent sensitive and noninvasive instruments to evaluate in vivo the metabolic trapping of radiopharmaceuticals. This study aimed to assess the imaging biodistribution of a [(99m)Tc]-radiolabelled new prototype bioconjugate composed of paclitaxel linked to hyaluronan (ONCOFID-P).
A small gamma camera providing high-resolution images was employed. Imaging of biodistribution following intravenous, intraperitoneal, intravesical and oral administration was carried out for a 2-h period in anesthetized mice receiving [(99m)Tc]ONCOFID-P. At the end of the observation time, radioactivity in organs was directly measured. As a control, groups of mice were treated with free [(3)H]paclitaxel given according to the same administration routes, and organ biodistribution of the drug was assessed after 2 h.
Intravenous inoculation of [(99m)Tc]ONCOFID-P was followed by a rapid and strong liver uptake. In fact, almost 80% of the imaging signal was detected in this organ 10 min after injection and such value remained constant thereafter, thus indicating that the bioconjugate given through the intravenous route could be well suited to targeting primary or metastatic liver neoplasias. Imaging of the bladder, abdomen and gastrointestinal tract after local administration disclosed that the radiolabelled compound remained confined to the cavities, suggesting a potential regional application for transitional bladder cell carcinomas, ovarian cancers and gastric tumors, respectively. Free [(3)H]paclitaxel biodistribution profoundly differed from that of [(99m)Tc]ONCOFID-P.
Conjugation of drugs with polymers results in new chemical entities characterized by a modified biodistribution pattern. Therefore, preclinical studies based on imaging analysis of such new compounds can suggest novel therapeutic applications.
伽马射线探测器是用于在体内评估放射性药物代谢捕获的灵敏且非侵入性的仪器。本研究旨在评估一种由紫杉醇与透明质酸连接而成的[(99m)Tc]放射性标记新型生物共轭物（ONCOFID-P）的成像生物分布。
使用一台能提供高分辨率图像的小型伽马相机。在接受[(99m)Tc]ONCOFID-P的麻醉小鼠中，分别经静脉、腹腔、膀胱内和口服给药后进行2小时的生物分布成像。观察期结束时，直接测量各器官中的放射性。作为对照，给小鼠组按相同给药途径给予游离[(3)H]紫杉醇，并在2小时后评估药物的器官生物分布。
静脉注射[(99m)Tc]ONCOFID-P后，肝脏迅速且强烈摄取。实际上，注射后10分钟该器官检测到近80%的成像信号，此后该值保持恒定，这表明经静脉途径给予的生物共轭物可能非常适合靶向原发性或转移性肝癌。局部给药后膀胱、腹部和胃肠道的成像显示，放射性标记化合物局限于腔内，分别提示对移行性膀胱细胞癌、卵巢癌和胃癌有潜在的局部应用价值。游离[(3)H]紫杉醇的生物分布与[(99m)Tc]ONCOFID-P有很大差异。
药物与聚合物共轭产生具有改变的生物分布模式特征的新化学实体。因此，基于对此类新化合物成像分析的临床前研究可提示新的治疗应用。
