Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results.
Development of an imaging-guided CEA-pretargeted radionuclide treatment of advanced colorectal cancer: first clinical results.
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开发成像引导的CEA-PRETARTARGITARGITAL核素治疗晚期结直肠癌：首次临床结果。
DOI：
10.1038/bjc.2013.376
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发表时间：
2013-08-20
影响因子：
8.8
通讯作者：
Oyen WJ
中科院分区：
文献类型：
--
作者：
Schoffelen R;Boerman OC;Goldenberg DM;Sharkey RM;van Herpen CM;Franssen GM;McBride WJ;Chang CH;Rossi EA;van der Graaf WT;Oyen WJ
放射标记抗体靶向癌症受到血液清除缓慢的限制。用非放射性标记的双特异性单克隆抗体（bsMAb）预先靶向，然后快速清除放射性标记的半抗原肽，可改善肿瘤定位。这项针对抗ceacam5 ×抗半抗原（HSG） bsMAb、TF2和放射性标记半抗原肽（IMP288）患者的首次预靶向研究的主要目标是评估转移性结直肠癌（CRC）患者的最佳预靶向条件和安全性。在4组5例患者中研究了不同的剂量计划：(1)缩短bsMAb和肽给药间隔（5天vs 1天），(2)增加TF2剂量（从75 mg增加到150 mg），(3)减少肽剂量（从100 μg减少到25 μg）。在确认111In-IMP288靶向肿瘤后，患者接受bsMAb/177Lu-IMP288周期治疗。在1小时内观察到放射性标记肽的快速和选择性肿瘤靶向，具有高肿瘤与组织的比率（24小时时bbb20）。bsMAb与肽和25 μg肽剂量间隔1天，肿瘤靶向性得到改善。高剂量177Lu-IMP288 （2.5-7.4 GBq）耐受性良好，有一些可控的TF2输注反应，10%接受177Lu-IMP288治疗的患者出现短暂的3-4级血小板减少症。这项I期研究首次证明了bsMAb TF2和放射性标记的IMP288对表达cea的结直肠癌患者的预靶向治疗是可行和安全的。使用这种预靶向方法，肿瘤被特异性和快速靶向。
Radiolabelled antibody targeting of cancer is limited by slow blood clearance. Pretargeting with a non-radiolabelled bispecific monoclonal antibody (bsMAb) followed by a rapidly clearing radiolabelled hapten peptide improves tumour localisation. The primary goals of this first pretargeting study in patients with the anti-CEACAM5 × anti-hapten (HSG) bsMAb, TF2, and the radiolabelled hapten-peptide, IMP288, were to assess optimal pretargeting conditions and safety in patients with metastatic colorectal cancer (CRC). Different dose schedules were studied in four cohorts of five patients: (1) shortening the interval between the bsMAb and peptide administration (5 days vs 1 day), (2) escalating the TF2 dose (from 75 to 150 mg), and (3) reducing the peptide dose (from 100 to 25 μg). After confirmation of tumour targeting by 111In-IMP288, patients were treated with a bsMAb/177Lu-IMP288 cycle. Rapid and selective tumour targeting of the radiolabelled peptide was visualised within 1 h, with high tumour-to-tissue ratios (>20 at 24 h). Improved tumour targeting was achieved with a 1-day interval between the administration of the bsMAb and the peptide and with the 25-μg peptide dose. High 177Lu-IMP288 doses (2.5–7.4 GBq) were well tolerated, with some manageable TF2 infusion reactions, and transient grades 3–4 thrombocytopaenia in 10% of the patients who received 177Lu-IMP288. This phase I study demonstrates for the first time that pretargeting with bsMAb TF2 and radiolabelled IMP288 in patients with CEA-expressing CRC is feasible and safe. With this pretargeting method, tumours are specifically and rapidly targeted.
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影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
45.3
作者：
Giantonio, Bruce J.;Catalano, Paul J.;Benson, Al B., III
通讯作者：
Benson, Al B., III
DOI：
10.1073/pnas.0600982103
发表时间：
2006-05-02
影响因子：
11.1
作者：
Rossi, EA;Goldenberg, DM;Chang, CH
通讯作者：
Chang, CH
影响因子：
64.8
作者：
REARDAN, DT;MEARES, CF;FRINCKE, JM
通讯作者：
FRINCKE, JM
影响因子：
9.3
作者：
Goldenberg, David M.;Rossi, Edmund A.;Chang, Chien-Hsing
通讯作者：
Chang, Chien-Hsing