整合素受体核素显像诊断乳腺癌骨转移病灶的实验研究

Experimental study of integrin α_vβ_3 micro positron emission tomography (micro PET)/CT imaging with ^(68)Ga-DOTA-RGD_2 in diagnosis of breast cancer osteolytic bone metastases

目的探讨^(68)镓-1,4,7,10一四氮杂环十二烷-l,4,7,10-四乙酸-(精氨酸-甘氨酸-天冬氨酸)2(^(68)Ga-DOTARGD_2)正电子发射microPET/CT显像探测乳腺癌骨转移病灶的价值。方法采用人乳腺癌骨转移细胞株(MDA-MB-231),在左心室进行细胞悬液注射并构建裸鼠乳腺癌骨转移模型,在其顶骨注射甲状旁腺激素(PTH)模拟溶骨型骨病变,设为RGD组和FDG组,每组6只,分别行^(68)Ga-DOTA-RGD_2和^(18)F-NaFmicroPET/CT显像,进行病理学检查验证。结果 PTH注射侧顶骨部位与周围正常顶骨~8Ga-DOTA-RGD_2放射性摄取比值为(4.18±0.57),显著高于FDG组18F-Na Fmicro PET/CT显像(1.24±0.28)(P<0.05)。^(68)Ga-DOTA-RGD_2microPET显像对骨转移病灶的检出率显著高于microCT显像(P<0.05)。结论^(68)Ga-DOTA-RGD_2整合素受体αvβ3显像可有效探测并定位乳腺癌骨转移病灶。

Objective To explore the value of integrin αvβ3 micro positron emission tomography （mieroPET）/CT imaging with ^68Ga-DOTA-RGD2 in diagnosis of breast cancer osteolytic bone metastases. Methods MDA-MB-231 was injected in left ventricle of hairless mice at the density of 1.0 × 10^7/mL. Animal model with parathyroid hormone （FFH）-induced osteolysis in the calvarium was established. Animals were randomly divided into RGD group （n = 10） and FDG group （n = 10）, and were detected by ^68Ga-DOTA-RGD2 microPET/CT and ^18F-NaFmicroPET/CT respectively. Animals were sacrificed and bone lesions were collected for pathological examination. Results Bone radiotracer uptake ratio of osteolytie lesion to normal calvrium （O/N） was （4.18 ± 0. 570） by ^68Ga- DOTA-RGD2, which was significantly higher than （ 1.24 ± 0.28 ） in group FDG by ^18F-NaFmicro- PET/CT imaging （P 〈 0.05 ）. Conclusion ^68 Ga-DOTA-RGD2 integrin receptor αvβ3 imaging can effectively detect breast cancer bone metastases and locate osteolytic lesions.