在动物模型中用177Lu-DOTA-酪氨酰3-奥曲肽进行小细胞肺癌的放射治疗。

Radiation therapy of small cell lung cancer with 177Lu-DOTA-Tyr3-octreotate in an animal model.

作者信息

Schmitt Anneli, Bernhardt Peter, Nilsson Ola, Ahlman Håkan, Kölby Lars, Maecke Helmut R, Forssell-Aronsson Eva

机构信息

Department of Radiation Physics, Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, Göteborg University, Göteborg, Sweden.

出版信息

J Nucl Med. 2004 Sep;45(9):1542-8.

PMID:15347722

Abstract

UNLABELLED

Small cell lung cancer (SCLC) is a tumor of neuroendocrine (NE) origin with very low survival rate. Somatostatin receptor scintigraphy using 111In-DTPA-octreotide (DTPA is diethylenetriaminepentaacetic acid) is a well-established method for the visualization of somatostatin receptor-expressing NE tumors. Recently, new combinations of radionuclides and somatostatin analogs have been investigated for therapeutic purposes. In this study, the somatostatin analog DOTA-Tyr3-octreotate (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid), labeled with the medium-energy electron emitter 177Lu (maximal electron energy = 498 keV, half-life = 6.6 d), was used for radiation therapy of human SCLC in an animal model.

METHODS

Nude mice, bearing tumors from the human SCLC cell line NCI-H69, were injected intravenously with 177Lu-DOTA-Tyr3-octreotate. Groups of animals (n = 5 or 6) were injected with 45-, 60-, and 120-MBq fractions and two 45-MBq fractions 48 h apart. Furthermore, 1 control group was treated with unlabeled DOTA-Tyr3-octreotate and another control group was not treated.

RESULTS

In both control groups, the tumor volumes were increased 2-fold in approximately 5 d. Treatment with 177Lu-DOTA-Tyr3-octreotate resulted in marked tumor regression with statistically significant tumor volume reduction after 1 wk (P < 0.001). The tumor growth delay time was dependent on the amount of injected activity for the groups with single injections, 26 d for 60 MBq and 40 d for 120 MBq. The best therapeutic effect was obtained in mice injected with 2 fractions of 45 MBq. The relative tumor volume after 1 mo was 0.004 +/- 0.004.

CONCLUSION

Radiation therapy with 177Lu-DOTA-Tyr3-octreotate on SCLC-bearing mice was successful. Since the experiments were performed on a human SCLC cell line xenografted to nude mice, the results may be clinically relevant and treatment with 177Lu-DOTA-Tyr3-octreotate could be a treatment alternative in this tumor disease that normally has a dismal prognosis.

摘要

未标记

小细胞肺癌（SCLC）是一种神经内分泌（NE）起源的肿瘤，生存率极低。使用111In - DTPA - 奥曲肽（DTPA是二乙三胺五乙酸）的生长抑素受体闪烁扫描是一种用于可视化表达生长抑素受体的NE肿瘤的成熟方法。最近，已对放射性核素和生长抑素类似物的新组合进行了治疗用途的研究。在本研究中，用中能电子发射体177Lu（最大电子能量 = 498 keV，半衰期 = 6.6天）标记的生长抑素类似物DOTA - Tyr3 - 奥曲肽（DOTA是1,4,7,10 - 四氮杂环十二烷 - N,N',N",N"'- 四乙酸）用于动物模型中人类SCLC的放射治疗。

方法

将携带人SCLC细胞系NCI - H69肿瘤的裸鼠静脉注射177Lu - DOTA - Tyr3 - 奥曲肽。动物组（n = 5或6）分别注射45、60和120 MBq剂量，以及相隔48小时的两个45 MBq剂量。此外，1个对照组用未标记的DOTA - Tyr3 - 奥曲肽治疗，另一个对照组不进行治疗。

结果

在两个对照组中，肿瘤体积在约5天内增加了2倍。用177Lu - DOTA - Tyr3 - 奥曲肽治疗导致肿瘤明显消退，1周后肿瘤体积有统计学意义的减小（P < 0.001）。对于单次注射的组，肿瘤生长延迟时间取决于注射活度的量，60 MBq组为26天，120 MBq组为40天。在注射两个45 MBq剂量的小鼠中获得了最佳治疗效果。1个月后的相对肿瘤体积为0.004±0.004。