Comparison of 177Lu-octreotate and 177Lu-octreotide for treatment in human neuroblastoma-bearing mice

被引：0

作者：

Romiani, A. ^{[1
,2
]}

Simonsson, K. ^{[1
,2
]}

Pettersson, D. ^{[1
,2
]}

Al-Awar, A. ^{[1
,2
]}

Rassol, N. ^{[1
,2
]}

Bakr, H. ^{[1
,2
,3
]}

Lind, D. E. ^{[2
,4
]}

Umapathy, G. ^{[2
,4
]}

Spetz, J. ^{[1
]}

Palmer, R. H. ^{[2
,4
]}

Hallberg, B. ^{[2
,4
]}

Helou, K. ^{[2
,5
]}

Forssell-Aronsson, E. ^{[1
,2
,3
,6
]}

机构：

[1] Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Med Radiat Sci, Gothenburg, Sweden

[2] Univ Gothenburg, Sahlgrenska Acad, Sahlgrenska Ctr Canc Res, Gothenburg, Sweden

[3] Sahlgrens Univ Hosp, Med Phys & Biomed Engn, Gothenburg, Sweden

[4] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Biochem & Cell Biol, Gothenburg, Sweden

[5] Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden

[6] Sahlgrens Univ Hosp, Dept Med Radiat Sci, SE-41345 Gothenburg, Sweden

来源：

HELIYON | 2024年 / 10卷 / 10期

基金：

瑞典研究理事会;

关键词：

Lutathera; Radionuclide therapy; High-risk neuroblastoma; Somatostatin analogs; Apoptosis; NUDE-MICE; TRANSCRIPTIONAL RESPONSE; TYROSINE KINASE; SOMATOSTATIN; RECEPTOR; ALK; BIODISTRIBUTION; ACTIVATION; APOPTOSIS; NEUROENDOCRINE;

D O I：

10.1016/j.heliyon.2024.e31409

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: Patients with high -risk neuroblastoma (NB) have a 5 -year event -free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of 177 Lu-octreotate and 177 Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes. Methods: The biodistribution of 177 Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of 177 Lu-octreotate or 177 Lu- octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR. Results: The activity concentration was generally lower in most tissues for 177 Lu-octreotide compared to 177 Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for 177 Lu-octreotide and 2.9 and 0.45 Gy/MBq for 177 Lu-octreotate, respectively. 177 Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes TNSFS8 , TNSFS10 , and TRADD were regulated after administration with 177 Lu-octreotate. Treatment with 177 Lu- octreotide yielded regulation of the pro-apoptotic genes CASP5 and TRADD , and of the antiapoptotic gene IL10 as well as the apoptosis-related gene TNF . Conclusion: 177 Lu-octreotide gave somewhat better anti -tumor effects than 177 Lu-octreotate. The similar effect observed in the treated groups with 177 Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti -tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.

引用

页数：13

共 72 条

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