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Correction to An N-Acetylgalactosamino Dendron-Clearing Agent for High-Therapeutic-Index DOTA-Hapten Pretargeted Radioimmunotherapy
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2021-01-24 , DOI: 10.1021/acs.bioconjchem.0c00686
Sarah M Cheal , Mitesh Patel , Guangbin Yang , Darren R Veach , Hong Xu , Hong-Fen Guo , Pat B Zanzonico , Donald B Axworthy , Nai-Kong V Cheung , Ouathek Ouerfelli , Steven M Larson

With apologies for the confusion, several systematic errors occurred in the organ radiation dosimetry of the [177Lu]LuDOTA-Bn, which were “propagated” at various points in the manuscript. The corrected radiation-absorbed dose estimates are specified below. Page 501. There is an error in the absorbed doses in the abstract. The correct doses should read as follows: Pretargeting [177Lu]LuDOTA-Bn with CCA α-16-DOTA-Y3+ to GPA33-expressing SW1222 human colorectal xenografts was highly effective, leading to absorbed doses of [177Lu]LuDOTA-Bn for blood, tumor, liver, spleen, and kidneys of 5.74, 229, 4.88, 2.68, and 6.52 cGy/MBq, respectively. Tumor-to-normal tissues absorbed-dose ratios (i.e., TIs) ranged from 40 (e.g., for blood and kidney) to about 550 for stomach. Page 504. There is an error in the absorbed doses in the Results and Discussion section. The correct doses should read as follows: The estimated absorbed doses (cGy/MBq) to tumor, blood, liver, and kidney for single-cycle PRIT plus dendron-CA were 229, 5.74 (TI: 40), 4.88 (TI: 47), and 6.52 (TI: 35), respectively (Table 2). In addition, absorbed doses were calculated for select tissues for DOTA-PRIT without dendron-CA by assuming that the respective areas under the curves (AUCs or residence times) and therefore the absorbed doses scaled as the 24-h %ID/g values (i.e., there was no difference in the 177Lu-activity kinetics with and without CA); the calculated estimated absorbed doses for tumor, blood, liver, and kidney were 291, 61.8 (TI: 4.7), 37.8 (TI: 7.7), and 19.1 (TI: 15), respectively. Therapeutic index (TI) is defined as estimated tumor/normal tissues absorbed dose ratio. Page 504. There is an error in the absorbed doses in Table 2. The correct doses should read as follows: Page 504. There is an error in the absorbed doses in the Results and Discussion section. The correct doses should read as follows: Therefore, we anticipate that effective and safe colorectal cancer therapy in xenografts in mice is feasible with DOTA-PRIT plus dendron-CA, since a tumor-absorbed dose of ∼73 Gy can be achieved with an administered activity of 32 MBq (with 184 cGy to blood (marrow) and 209 cGy to kidney, which are below benchmark maximum tolerated doses (MTDs) based on human normal-tissue radiation dose tolerance estimates derived from clinical observations of 250 cGy and 2,000 cGy for bone marrow and kidney, respectively.21 Furthermore, we estimate that the maximum tolerated pretargeted [177Lu] LuDOTA-Bn activity is 43 MBq, with the bone marrow as the dose-limiting organ. At this activity, the estimated absorbed dose delivered to tumor would be 9,850 cGy (99 Gy), with 247 cGy to blood (marrow) and 280 cGy to kidney. This article has not yet been cited by other publications.

中文翻译:

用于高治疗指数 DOTA-Hapten 预靶向放射免疫疗法的 N-乙酰半乳糖胺树突清除剂的校正

对造成的混淆表示歉意,[177Lu]LuDOTA-Bn 的器官辐射剂量测定中出现了几个系统错误,这些错误在手稿的各个点“传播”。校正后的辐射吸收剂量估计值如下所述。第 501 页。摘要中的吸收剂量存在错误。正确的剂量应如下所示:将 [177Lu]LuDOTA-Bn 与 CCA α-16-DOTA-Y3+ 预靶向到表达 GPA33 的 SW1222 人结直肠异种移植物是非常有效的,导致吸收剂量的 [177Lu]LuDOTA-Bn 用于血液,肿瘤、肝脏、脾脏和肾脏分别为 5.74、229、4.88、2.68 和 6.52 cGy/MBq。肿瘤与正常组织的吸收剂量比(即,TIs)范围从 40(例如,血液和肾脏)到胃的约 550。第 504 页。结果和讨论部分的吸收剂量存在错误。正确剂量应如下所示:单周期 PRIT 加树突-CA 对肿瘤、血液、肝脏和肾脏的估计吸收剂量 (cGy/MBq) 分别为 229、5.74 (TI: 40)、4.88 (TI: 47) ) 和 6.52 (TI: 35) 分别为(表 2)。此外,针对 DOTA-PRIT 的选定组织计算了吸收剂量通过假设曲线下的相应面积(AUC 或停留时间)以及因此吸收剂量按 24 小时 %ID/g 值缩放(即,在177含和不含 CA 的 Lu 活性动力学);计算出的肿瘤、血液、肝脏和肾脏的估计吸收剂量分别为 291、61.8 (TI: 4.7)、37.8 (TI: 7.7) 和 19.1 (TI: 15)。治疗指数 (TI) 定义为估计的肿瘤/正常组织吸收剂量比。第 504 页。表 2 中的吸收剂量存在错误。正确的剂量应如下所示: 第 504 页。结果和讨论部分的吸收剂量存在错误。正确的剂量应如下所示:因此,我们预计使用 DOTA-PRIT 加 dendron-CA 对小鼠异种移植物进行有效和安全的结直肠癌治疗是可行的,因为使用给药可以实现约 73 Gy 的肿瘤吸收剂量32 MBq 的活性(血液(骨髓)为 184 cGy,肾脏为 209 cGy,21此外,我们估计最大耐受的预靶向 [ 177 Lu] LuDOTA-Bn 活性为 43 MBq,其中骨髓是剂量限制器官。在此活动中,估计递送至肿瘤的吸收剂量为 9,850 cGy(99 Gy),其中血液(骨髓)为 247 cGy,肾脏为 280 cGy。这篇文章尚未被其他出版物引用。
更新日期:2021-02-17
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