前列腺特异性膜抗原有望成为使用[177Lu]Lu-PSMA-I&T 对三阴性乳腺癌进行内源性放射治疗的血管靶点

IF 6.1 1区 医学 Q1 ONCOLOGY Breast Cancer Research Pub Date : 2024-02-20 DOI:10.1186/s13058-024-01787-9
Amelie Heesch, Alexandru Florea, Jochen Maurer, Pardes Habib, Laura S. Werth, Thomas Hansen, Elmar Stickeler, Sabri E. M. Sahnoun, Felix M. Mottaghy, Agnieszka Morgenroth
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引用次数: 0

摘要

前列腺特异性膜抗原(PSMA)在三阴性乳腺癌(TNBC)血管上的过度表达为使用[177Lu]Lu-PSMA-I&T进行靶向内放射治疗提供了一个前景广阔的途径。本研究旨在评估和比较单剂量与分剂量[177Lu]Lu-PSMA-I&T在TNBC正位模型中的疗效。Rj:NMRI-Foxn1nu/nu小鼠是MDA-MB-231异种移植物的受体。单剂量组接受1 × 60 ± 5 MBq剂量的[177Lu]Lu-PSMA-I&T治疗,分剂量组接受4 × 15 ± 2 MBq剂量的[177Lu]Lu-PSMA-I&T治疗,间隔7天。对照组接受 0.9% NaCl。使用[18F]FDG-PET/CT监测肿瘤进展。体内外分析包括免疫染色、TUNEL染色、H&E染色、显微自动放射摄影和自动放射摄影。单剂量组(p < 0.001)和分剂量组(p < 0.001)的肿瘤体积明显较小。肿瘤生长抑制率分别为 38%(单剂量)和 30%(分次剂量)。与对照组相比,治疗组的中位生存期明显延长(单剂量组、分剂量组和对照组的中位生存期分别为31天、28天和19天)。[177Lu]Lu-PSMA-I&T能缩小存活肿瘤区域的大小。我们进一步证实,[177Lu]Lu-PSMA-I&T 能与肿瘤相关血管特异性结合。这项研究凸显了[177Lu]Lu-PSMA-I&T在TNBC内源性放射治疗中的潜力。
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The prostate-specific membrane antigen holds potential as a vascular target for endogenous radiotherapy with [177Lu]Lu-PSMA-I&T for triple-negative breast cancer
Overexpression of prostate-specific membrane antigen (PSMA) on the vasculature of triple-negative breast cancer (TNBC) presents a promising avenue for targeted endogenous radiotherapy with [177Lu]Lu-PSMA-I&T. This study aimed to assess and compare the therapeutic efficacy of a single dose with a fractionated dose of [177Lu]Lu-PSMA-I&T in an orthotopic model of TNBC. Rj:NMRI-Foxn1nu/nu mice were used as recipients of MDA-MB-231 xenografts. The single dose group was treated with 1 × 60 ± 5 MBq dose of [177Lu]Lu-PSMA-I&T, while the fractionated dose group received 4 × a 15 ± 2 MBq dose of [177Lu]Lu-PSMA-I&T at 7 day intervals. The control group received 0.9% NaCl. Tumor progression was monitored using [18F]FDG-PET/CT. Ex vivo analysis encompassed immunostaining, TUNEL staining, H&E staining, microautoradiography, and autoradiography. Tumor volumes were significantly smaller in the single dose (p < 0.001) and fractionated dose (p < 0.001) groups. Tumor growth inhibition rates were 38% (single dose) and 30% (fractionated dose). Median survival was notably prolonged in the treated groups compared to the control groups (31d, 28d and 19d for single dose, fractionated dose and control, respectively). [177Lu]Lu-PSMA-I&T decreased the size of viable tumor areas. We further demonstrated, that [177Lu]Lu-PSMA-I&T binds specifically to the tumor-associated vasculature. This study highlights the potential of [177Lu]Lu-PSMA-I&T for endogenous radiotherapy of TNBC.
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来源期刊
Breast Cancer Research
Breast Cancer Research 医学-肿瘤学
自引率
0.00%
发文量
76
期刊介绍: Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, editorials and reports. Open access research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal publishes preclinical, translational and clinical studies with a biological basis, including Phase I and Phase II trials.
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