Strickland D K, Vaidyanathan G, Zalutsky M R
Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710.
Cancer Res. 1994 Oct 15;54(20):5414-9.
Radioiodinated m-iodobenzylguanidine (MIBG) has been used with only limited success for the treatment of neural crest tumors including neuroblastoma. Use of an MIBG analogue labeled with 211At could be advantageous because of the shorter range and higher linear energy transfer of its alpha-particle emissions compared with the beta-particles emitted by 131I. The potential utility of m-[211At]astatobenzylguanidine for the treatment of neuroblastoma was investigated in vitro using 3 human neuroblastoma cell lines known to take up MIBG [SK-N-SH, SK-N-BE(2C), and SK-SY5Y] and a control line lacking MIBG uptake (SK-N-MC). Maximum binding of m-[211At]astatobenzylguanidine ([211At] MABG) to 5 x 10(5) cells after a 2-h incubation ranged from 61% for SK-N-SH to 1% for SK-N-MC. Using a limiting dilution clonogenic assay, the cytotoxicity for SK-N-SH cells of [211At]MABG was compared with [211At]astatide and no-carrier-added [131I]MIBG. A D0 of 5.8 nCi/ml was calculated for [211At]MABG compared with 482 nCi/ml for [211At] astatide, indicating a more than 80-fold enhanced cytotoxicity for the specifically targeted alpha-particles of [211At]MABG. For [211At]MABG, the D0 corresponded to only 6.4 211At atoms bound/cell compared with 9000 atoms/cell for no-carrier-added [131I]MIBG. The D0 values measured for [211At]MABG treatment of SK-SY5Y, SK-N-BE(2C), and SK-N-MC cells were 50, 5.8, and 11,043 nCi/ml, respectively, corresponding to 7.04, 6.46, and 171.79 211At atoms bound/cell. In conclusion, these results have demonstrated that [211At]MABG is considerably more cytotoxic than [131I]MIBG and that [211At]MABG could have great potential as a radiotherapeutic agent for the treatment of neuroblastoma.
放射性碘化间碘苄胍（MIBG）用于治疗包括神经母细胞瘤在内的神经嵴肿瘤，效果有限。使用标记有砹-211的MIBG类似物可能具有优势，因为与碘-131发射的β粒子相比，其α粒子发射的射程更短且线能量传递更高。使用3种已知摄取MIBG的人神经母细胞瘤细胞系[SK-N-SH、SK-N-BE(2C)和SK-SY5Y]以及一个缺乏MIBG摄取的对照细胞系（SK-N-MC），在体外研究了间-[砹-211]砹苄胍治疗神经母细胞瘤的潜在效用。孵育2小时后，间-[砹-211]砹苄胍（[211At]MABG）与5×10(5)个细胞的最大结合率在SK-N-SH细胞中为61%，在SK-N-MC细胞中为1%。使用极限稀释克隆形成试验，将[211At]MABG对SK-N-SH细胞的细胞毒性与[211At]砹化物和无载体添加的[131I]MIBG进行比较。计算得出[211At]MABG的D0为5.8 nCi/ml，而[211At]砹化物为482 nCi/ml，这表明[211At]MABG特异性靶向的α粒子的细胞毒性增强了80多倍。对于[劳-211]MABG，D0仅相当于每个细胞结合6.4个砹-211原子，而无载体添加的[131I]MIBG为每个细胞9000个原子。[211At]MABG处理SK-SY5Y、SK-N-BE(2C)和SK-N-MC细胞测得的D0值分别为50、5.8和11,043 nCi/ml，分别相当于每个细胞结合7.04、6.46和171.79个砹-211原子。总之，这些结果表明，[211At]MABG的细胞毒性比[131I]MIBG大得多，并且[211At]MABG作为治疗神经母细胞瘤的放射治疗剂可能具有巨大潜力。
