Importance:131I-metaiodobenzylguanidine(131I-mIBG)has a significant targeted antitumor effect for neuroblastoma.However,currently there is a paucity of data for the use of 131I-mIBG as a"front-line"therapeut...Importance:131I-metaiodobenzylguanidine(131I-mIBG)has a significant targeted antitumor effect for neuroblastoma.However,currently there is a paucity of data for the use of 131I-mIBG as a"front-line"therapeutic agent in those patients with newly diagnosed high-risk neuroblastoma as part of the conditioning regimen for myeloablative chemotherapy(MAC).Objective:To evaluate the feasibility of upfront consolidation treatment with 131I-mIBG plus MAC and hematopoietic stem cell transplantation(HSCT)in high-risk neuroblastoma patients.Methods:A retrospective,single-center study was conducted from 2003-2019 on newly diagnosed high-risk neuroblastoma patients without progressive disease(PD)after the completion of induction therapy.They received 131I-mIBG infusion and MAC followed by HSCT.Results:A total of 24 high-risk neuroblastoma patients were enrolled with a median age of 3.0 years at diagnosis.After receiving this sequential consolidation treatment,3 of 13 patients who were in partial response(PR)before 131I-mIBG treatment achieved either complete response(CR)(n=1)or very good partial response(VGPR)(n=2)after HSCT.With a median follow-up duration of 13.0 months after 131I-mIBG therapy,the 5-year event-free survival and overall survival rates estimated were 29%and 38%for the entire cohort,and 53%and 67%for the patients who were in CR/VGPR at the time of 131I-mIBG treatment.Interpretation:Upfront consolidation treatment with 131I-mIBG plus MAC and HSCT is feasible and tolerable in high-risk neuroblastoma patients,however the survival benefit of this 131I-mIBG regimen is only observed in the patients who were in CR/VGPR at the time of 131I-mIBG treatment.展开更多
Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its s...Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its short retention time in target cells. To prolong the retention of ^131I-MIBG in target cells, we infected hepatocarcinoma （HepG2） cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 （VMAT2） genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET- expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher ^131I-MIBG uptake than controls. Two hours after removal of ^131I-MIBG-containing medium, 25.4% efflux was observed in NET- VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer ^131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after ^131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased ^131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.展开更多
文摘Importance:131I-metaiodobenzylguanidine(131I-mIBG)has a significant targeted antitumor effect for neuroblastoma.However,currently there is a paucity of data for the use of 131I-mIBG as a"front-line"therapeutic agent in those patients with newly diagnosed high-risk neuroblastoma as part of the conditioning regimen for myeloablative chemotherapy(MAC).Objective:To evaluate the feasibility of upfront consolidation treatment with 131I-mIBG plus MAC and hematopoietic stem cell transplantation(HSCT)in high-risk neuroblastoma patients.Methods:A retrospective,single-center study was conducted from 2003-2019 on newly diagnosed high-risk neuroblastoma patients without progressive disease(PD)after the completion of induction therapy.They received 131I-mIBG infusion and MAC followed by HSCT.Results:A total of 24 high-risk neuroblastoma patients were enrolled with a median age of 3.0 years at diagnosis.After receiving this sequential consolidation treatment,3 of 13 patients who were in partial response(PR)before 131I-mIBG treatment achieved either complete response(CR)(n=1)or very good partial response(VGPR)(n=2)after HSCT.With a median follow-up duration of 13.0 months after 131I-mIBG therapy,the 5-year event-free survival and overall survival rates estimated were 29%and 38%for the entire cohort,and 53%and 67%for the patients who were in CR/VGPR at the time of 131I-mIBG treatment.Interpretation:Upfront consolidation treatment with 131I-mIBG plus MAC and HSCT is feasible and tolerable in high-risk neuroblastoma patients,however the survival benefit of this 131I-mIBG regimen is only observed in the patients who were in CR/VGPR at the time of 131I-mIBG treatment.
基金We thank Yuanyou Yang, PhD, for helping in the preparation of ^131I- MIBG. This study was fimded by the National Natural Science Foundation of China （No. 81271602）.
文摘Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its short retention time in target cells. To prolong the retention of ^131I-MIBG in target cells, we infected hepatocarcinoma （HepG2） cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 （VMAT2） genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET- expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher ^131I-MIBG uptake than controls. Two hours after removal of ^131I-MIBG-containing medium, 25.4% efflux was observed in NET- VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer ^131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after ^131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased ^131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.
