Takakusagi Yoichi, Sugyo Aya, Tsuji Atsushi B, Sudo Hitomi, Yasunaga Masahiro, Matsumura Yasuhiro, Sugawara Fumio, Sakaguchi Kengo, Higashi Tatsuya
Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), 4-9-1 Inage, Chiba 263-8555, Japan; Institute for Quantum Life Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQLS), 4-9-1 Inage, Chiba 263-8555, Japan.
Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum and Radiological Science and Technology (QST-iQMS), 4-9-1 Inage, Chiba 263-8555, Japan.
Transl Oncol. 2022 Jan;15(1):101285. doi: 10.1016/j.tranon.2021.101285. Epub 2021 Nov 25.
α-Sulfoquinovosylacyl-1,3-propanediol (SQAP) is a semi-synthetic derivative of natural sulfoglycolipid that sensitizes tumors to external-beam radiotherapy. How SQAP affects internal radiotherapy, however, is not known. Here, we investigated the effects of SQAP for radioimmunotherapy (RIT) targeting tissue factor (TF) in a stroma-rich refractory pancreatic cancer mouse model, BxPC-3. A low dose of SQAP (2 mg/kg) increased tumor uptake of the In-labeled anti-TF antibody 1849, indicating increased tumor perfusion. The addition of SQAP enhanced the growth-inhibitory effect of Y-labeled 1849 without leading to severe body weight changes, allowing for the dose of Y-labeled 1849 to be reduced to half that when used alone. Histologic analysis revealed few necrotic and apoptotic cells, but Ki-67-positive proliferating cells and increased vascular formation were detected. These results suggest that the addition of a low dose of SQAP may improve the therapeutic efficacy of TF-targeted RIT by increasing tumor perfusion, even for stroma-rich refractory pancreatic cancer.
α-磺基喹喔啉酰基-1,3-丙二醇(SQAP)是一种天然硫糖脂的半合成衍生物,可使肿瘤对体外放疗敏感。然而,SQAP如何影响内放疗尚不清楚。在此,我们在富含基质的难治性胰腺癌小鼠模型BxPC-3中研究了SQAP对靶向组织因子(TF)的放射免疫治疗(RIT)的影响。低剂量的SQAP(2毫克/千克)增加了铟标记的抗TF抗体1849的肿瘤摄取,表明肿瘤灌注增加。添加SQAP增强了钇标记的1849的生长抑制作用,且未导致严重的体重变化,使得钇标记的1849的剂量可降至单独使用时的一半。组织学分析显示坏死和凋亡细胞很少,但检测到Ki-67阳性增殖细胞和血管形成增加。这些结果表明,即使对于富含基质的难治性胰腺癌,添加低剂量的SQAP也可能通过增加肿瘤灌注来提高TF靶向RIT的治疗效果。