联合（177）镥-多胺多羧基大环配体-8-氨基辛酰基环六肽-蛙皮素（7-14）氨基甘氨酰胺受体靶向放疗与化疗在人前列腺癌PC-3细胞异种移植SCID小鼠中的评估
Evaluation of combined (177)Lu-DOTA-8-AOC-BBN (7-14)NH(2) GRP receptor-targeted radiotherapy and chemotherapy in PC-3 human prostate tumor cell xenografted SCID mice.
作者信息
Johnson Christopher V, Shelton Tiffani, Smith Charles J, Ma Lixin, Perry Michael C, Volkert Wynn A, Hoffman Timothy J
机构信息
Department of Veterinary Pathobiology, University of Missouri-Columbia, Columbia, MO., Harry S. Truman Memorial Veterans Hospital, Columbia, MO 65201-5275, USA.
出版信息
Cancer Biother Radiopharm. 2006 Apr;21(2):155-66. doi: 10.1089/cbr.2006.21.155.
The focus of this study was to evaluate the therapeutic benefit of combined gastrin-releasing peptide (GRP) receptor-targeted radiotherapy (TRT) with chemotherapy, using the PC-3 xenograft severe combined immunodeficiency (SCID) mouse model. (177)Lu-DOTA-8-AOC-BBN(7-14)NH(2) is a radiotherapeutic peptide that specifically targets the gastrin-releasing peptide receptor overexpressed on primary and metastatic prostate cancer. The chemotherapeutic agents, docetaxel and estramustine, were administered as single agents or in combination with the receptor-targeted radiotherapeutic agent. Combination receptor TRT/chemotherapy studies were begun 21 days postxenografting and were conducted as multiple-dose trials. The GRP receptor TRT agent was administered every 14 days, and single and combination chemotherapy dose regimens were given weekly. Tumor size, body weight, and body condition score were evaluated twice-weekly and a hematology profile once-weekly. Therapy study tumor volumes were evaluated by way of a repeated measures analysis of variance (ANOVA). Tumor volume measurements at 12 days postdose administration demonstrated a statistically significant (two-tailed P-value <0.05) tumor growth suppression in all experimental groups receiving GRP receptor-targeted radiotherapy, when compared to the control group. The two combined GRP receptor TRT/chemotherapy treatment groups demonstrated the greatest tumor growth suppression of all treatment groups. In comparing the two combined GRP receptor TRT/chemotherapy groups to the GRP receptor TRT alone group, a statistically significant difference was demonstrated for the combined groups by day 30, postdose administration. These data demonstrate that GRP receptor-targeted radiation therapy, using (177)Lu-DOTA-8-AOC-BBN(7-14)NH(2), used either alone or in combination with conventional chemotherapy, can suppress the growth of androgen- independent prostate cancer (AIPC).
本研究的重点是使用PC-3异种移植严重联合免疫缺陷（SCID）小鼠模型，评估胃泌素释放肽（GRP）受体靶向放疗（TRT）与化疗联合治疗的益处。（177）Lu-DOTA-8-AOC-BBN（7-14）NH₂是一种放射治疗肽，可特异性靶向原发性和转移性前列腺癌中过度表达的胃泌素释放肽受体。化疗药物多西他赛和雌莫司汀作为单一药物或与受体靶向放射治疗药物联合使用。联合受体TRT/化疗研究在异种移植后21天开始，作为多剂量试验进行。GRP受体TRT药物每14天给药一次，单一和联合化疗剂量方案每周给药一次。每周两次评估肿瘤大小、体重和身体状况评分，每周一次评估血液学指标。通过重复测量方差分析（ANOVA）评估治疗研究中的肿瘤体积。给药后12天的肿瘤体积测量结果表明，与对照组相比，所有接受GRP受体靶向放疗的实验组中肿瘤生长均受到统计学显著抑制（双尾P值<0.05）。两个联合GRP受体TRT/化疗治疗组在所有治疗组中表现出最大的肿瘤生长抑制。在将两个联合GRP受体TRT/化疗组与单独使用GRP受体TRT组进行比较时，给药后30天联合组显示出统计学显著差异。这些数据表明，使用（177）Lu-DOTA-8-AOC-BBN（7-14）NH₂的GRP受体靶向放射治疗，单独使用或与传统化疗联合使用，均可抑制雄激素非依赖性前列腺癌（AIPC）的生长。
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