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采用串联[(90)钇]多胺螯合奥曲肽和[(177)镥]多胺螯合奥曲肽治疗对传统疗法难治的神经内分泌肿瘤:初步结果

Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu] DOTA-TATE of neuroendocrine tumors refractory to conventional therapy: preliminary results.

作者信息

Seregni E, Maccauro M, Coliva A, Castellani M R, Bajetta E, Aliberti G, Vellani C, Chiesa C, Martinetti A, Bogni A, Bombardieri E

机构信息

Nuclear Medicine, National Cancer Institute, Milan, Italy.

出版信息

Q J Nucl Med Mol Imaging. 2010 Feb;54(1):84-91.

Abstract

AIM

Neuroendocrine tumors over-express somatostatin receptors and literature data have demonstrated the efficacy of the peptide receptor radionuclide therapy with somatostatin analogues labelled with high activities of b-emitting radioisotopes, such as (90)Y and (177)Lu. Yttrium-90 is a pure high energy b-emitter while (177)Lu is a b/g emitter of medium energy. We decided to evaluate an original tandem treatment based on administration of radiolabeled [DOTA(0),Tyr(3)]octreotate (DOTA-TATE) alternating (177)Lu and 90Y. Aim of this study was to evaluate the feasibility, the efficacy and the toxicity of this treatment in neuroendocrine tumors expressing somatostatin receptors relapsed or refractory to conventional therapies.

METHODS

Patients were treated with four therapeutic cycles alternating [(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). Dosimetric evaluation after administration of [(177)Lu]DOTA-TATE allows to calculate the absorbed doses in healthy organs. Blood samples were collected at 5 min, 1, 6, 24, 48, 72, 96 h and scintigraphy was performed once a day for four days after administration. Toxicity was evaluated considering hematological parameters and renal toxicity was evaluated also by the glomerular filtration rate (GFR). Efficacy related with RECIST criteria.

RESULTS

Up to now 26 patients entered the study and 16 patients completed all cycles. Treatment was well tolerated with no adverse event registered. No damage to healthy organs was revealed in accordance with the calculated absorbed doses. We had a partial response in 10/15 patients evaluated three months after the fourth treatment.

CONCLUSIONS

Up to now only a few patients participated in and concluded this study; preliminary results are encouraging and indicate the feasibility of the study.

摘要

目的

神经内分泌肿瘤过度表达生长抑素受体,文献数据已证明使用标记有高活度发射β射线放射性核素(如钇-90和镥-177)的生长抑素类似物进行肽受体放射性核素治疗的疗效。钇-90是一种纯高能β发射体,而镥-177是一种中能β/γ发射体。我们决定评估一种基于交替给予放射性标记的[DOTA(0),Tyr(3)]奥曲肽(DOTA-TATE)(镥-177和钇-90)的原创串联治疗方法。本研究的目的是评估这种治疗方法在对传统疗法复发或难治的表达生长抑素受体的神经内分泌肿瘤中的可行性、疗效和毒性。

方法

患者接受四个治疗周期,交替给予[镥-177]DOTA-TATE(5.55 GBq)和[钇-90]DOTA-TATE(2.6 GBq)。给予[镥-177]DOTA-TATE后的剂量学评估可计算健康器官的吸收剂量。在给药后5分钟、1、6、24、48、72、96小时采集血样,并在给药后连续四天每天进行一次闪烁扫描。根据血液学参数评估毒性,通过肾小球滤过率(GFR)评估肾毒性。疗效根据实体瘤疗效评价标准(RECIST)进行评估。

结果

截至目前,26例患者进入研究,16例患者完成了所有周期。治疗耐受性良好,未记录到不良事件。根据计算的吸收剂量,未发现对健康器官的损害。在第四次治疗三个月后评估的15例患者中,有10例出现部分缓解。

结论

截至目前,仅有少数患者参与并完成了本研究;初步结果令人鼓舞,表明该研究具有可行性。

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