Schmitt Anneli, Bernhardt Peter, Nilsson Ola, Ahlman Håkan, Kölby Lars, Forssell-Aronsson Eva
Department of Radiation Physics, Göteborg University, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden.
Cancer Biother Radiopharm. 2005 Apr;20(2):231-6. doi: 10.1089/cbr.2005.20.231.
(177)Lu-DOTA-Tyr(3)-octreotate is a candidate radiopharmaceutical for the therapy of somatostatin receptor (sstr)-positive small cell lung cancer (SCLC). Scintigraphy of lung tumors is made with 2 alternative somatostatin analogs, (111)In-DTPA-octreotide or (99m)Tc-depreotide. The aim of this study was to compare the biodistribution of these 3 radiopharmaceuticals in SCLC xenografted to nude mice.
Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were intravenously injected with 10 MBq (2.4 microg) (99m)Tc-depreotide and 2 MBq (0.5 microg) (111)In-DTPA-octreotide simultaneously. The activity concentration (%IA/g) was measured in tumor and normal tissue at 2, 4, and 24 hours postinjection (hpi). The results were compared with earlier published biodistribution data of 3 MBq (0.7 microg) (177)Lu-DOTA-Tyr(3)-octreotate in the same animal model.
The activity concentration of (111)In-DTPAoctreotide in tumor was higher than the activity concentration of (99m)Tc-depreotide at 2-24 hpi, p < 0.05. The highest tumor uptake at 24 hpi was, however, found for (177)Lu-DOTA-Tyr(3)-octreotate. The activity concentration of (99m)Tc-depreotide was significantly higher in the heart, lungs, liver, the salivary glands, spleen, and bone marrow than for (111)In-DTPA-octreotide at 2-24 hpi. Saturation of the somatostatin receptors may have influenced the uptake in tumor and sstr-positive normal tissues.
The low tumor-to-lung and tumor-to-liver activity concentration ratios for (99m)Tc-depreotide could result in a lower detection rate of SCLC with this compound versus (111)In-DTPA-octreotide. (177)Lu-DOTA-Tyr(3)-octreotate gave the highest tumor-activity concentration, and has, thus, the best properties for therapy.
（177）镥 - DOTA - 酪氨酰（3） - 奥曲肽是一种用于治疗生长抑素受体（sstr）阳性小细胞肺癌（SCLC）的放射性药物候选物。用两种替代的生长抑素类似物，即（111）铟 - DTPA - 奥曲肽或（99m）锝 - 替曲膦进行肺肿瘤的闪烁显像。本研究的目的是比较这三种放射性药物在移植到裸鼠体内的SCLC中的生物分布。
将携带人SCLC细胞系NCI - H69肿瘤的裸鼠静脉内同时注射10 MBq（2.4微克）（99m）锝 - 替曲膦和2 MBq（0.5微克）（111）铟 - DTPA - 奥曲肽。在注射后2、4和24小时（hpi）测量肿瘤和正常组织中的活度浓度（%IA/g）。将结果与先前发表的在同一动物模型中3 MBq（0.7微克）（177）镥 - DOTA - 酪氨酰（3） - 奥曲肽的生物分布数据进行比较。
在2 - 24 hpi时，（111）铟 - DTPA - 奥曲肽在肿瘤中的活度浓度高于（99m）锝 - 替曲膦的活度浓度，p < 0.05。然而，在24 hpi时，（177）镥 - DOTA - 酪氨酰（3） - 奥曲肽的肿瘤摄取最高。在2 - 24 hpi时，（99m）锝 - 替曲膦在心脏、肺、肝脏、唾液腺、脾脏和骨髓中的活度浓度明显高于（111）铟 - DTPA - 奥曲肽。生长抑素受体的饱和可能影响了肿瘤和sstr阳性正常组织中的摄取。
（99m）锝 - 替曲膦的低肿瘤与肺以及肿瘤与肝脏的活度浓度比可能导致与（111）铟 - DTPA - 奥曲肽相比，用该化合物检测SCLC的率较低。（177）镥 - DOTA - 酪氨酰（3） - 奥曲肽的肿瘤活度浓度最高，因此具有最佳的治疗特性。
