Mitsuyuki Kosuke, Watabe Tadashi, Naka Sadahiro, Liu Yuwei, Tatsumi Mitsuaki, Shimosegawa Eku, Kato Hiroki
Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Suita 565-0871, Japan.
Department of Radiology, Osaka University Hospital, Suita 565-0871, Japan.
Diagnostics (Basel). 2021 Jul 19;11(7):1295. doi: 10.3390/diagnostics11071295.
Tumor blood flow (TBF) is related to drug delivery and hypoxia, both of which can impact the efficacy of anti-cancer therapies. Although integrin αβ expression is related to tumor angiogenesis, it remains unclear whether the degree of angiogenesis affects TBF. This study aimed to evaluate the expression of integrin αβ in mouse tumor models using [Ga]Ga-DOTA-c(RGDfK) peptide positron emission tomography (PET) and immunohistochemical staining. PET studies were conducted using mouse C6 glioma models and MIA PaCa-2 ( = 6 each). The [Ga]Ga-DOTA-c(RGDfK) peptide was injected via the tail vein (2.17 ± 0.28 MBq), and 10 min static PET scans were performed. Immunohistochemical analysis was conducted using an integrin αβ antibody. [Ga]Ga-DOTA-c(RGDfK) peptide PET revealed higher uptake of the radiotracer in C6 gliomas than in MIA PaCa-2 tumors. The mean standardized uptake value was significantly higher in C6 gliomas (0.35 ± 0.058) than in MIA PaCa-2 tumors (0.17 ± 0.045). Histological analysis revealed intense integrin αβ expression in the C6 gliomas, whereas the MIA PaCa-2 tumors had low expression levels. This study showed that the expression of integrin αβ can be differentiated by the [Ga]Ga-DOTA-c(RGDfK) peptide, suggesting the potential applicability of this peptide in the evaluation of the relationship between angiogenesis and TBF.
肿瘤血流(TBF)与药物递送和缺氧有关,这两者都会影响抗癌治疗的疗效。尽管整合素αβ的表达与肿瘤血管生成有关,但血管生成程度是否影响TBF仍不清楚。本研究旨在使用[镓]镓-DOTA-c(RGDfK)肽正电子发射断层扫描(PET)和免疫组织化学染色评估整合素αβ在小鼠肿瘤模型中的表达。使用小鼠C6胶质瘤模型和MIA PaCa-2(各6只)进行PET研究。通过尾静脉注射[镓]镓-DOTA-c(RGDfK)肽(2.17±0.28 MBq),并进行10分钟的静态PET扫描。使用整合素αβ抗体进行免疫组织化学分析。[镓]镓-DOTA-c(RGDfK)肽PET显示C6胶质瘤中放射性示踪剂的摄取高于MIA PaCa-2肿瘤。C6胶质瘤的平均标准化摄取值(0.35±0.058)显著高于MIA PaCa-2肿瘤(0.17±0.045)。组织学分析显示C6胶质瘤中整合素αβ表达强烈,而MIA PaCa-2肿瘤表达水平较低。本研究表明,[镓]镓-DOTA-c(RGDfK)肽可区分整合素αβ的表达,提示该肽在评估血管生成与TBF关系方面具有潜在的适用性。