Quantitative [Fe]MRI determination of the dynamics of PSMA-targeted SPIONs discriminates among prostate tumor xenografts based on their PSMA expression.

Quantitative [Fe]MRI determination of the dynamics of PSMA-targeted SPIONs discriminates among prostate tumor xenografts based on their PSMA expression.
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DOI:
10.1002/jmri.25935
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发表时间:
2018-08
期刊:
Journal of magnetic resonance imaging : JMRI
影响因子:
--
通讯作者:
Sillerud LO
Sillerud LO
中科院分区:
其他
文献类型:
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作者:
Sillerud LO

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需要一种用于铁浓度磁共振成像的定量MRI方法,其适合于测量靶向超顺磁性氧化铁纳米颗粒(SPION)向肿瘤的递送。将我们新开发的[Fe]MRI方法应用于抗前列腺特异性膜抗原(PSMA)结合SPION在裸鼠人前列腺肿瘤异种移植物中的铁动力学的空间和时间定量成像。纵向45只哈兰Sprague道利无胸腺裸鼠,其携带来自人前列腺肿瘤细胞系的PSMA阳性LNCaP、C4-2和PSMA阴性DU 145肿瘤的异种移植物。1.0 Tesla/ T1和T2加权自旋回波图像强度和对比度测量学生t检验肿瘤内的SPION扩散系数为D = 44.8 ± 2.4 × 10-6 mm 2/sec。PSMA阳性LNCaP和C4-2肿瘤吸收的铁与尾静脉注射剂量(60 nmol-1.6 μ mol)成比例;在抗PSMA结合SPION中注射1 μ mol铁导致肿瘤[Fe]为76 μM。即使在1.6微摩尔的最高铁剂量下,PSMA阴性DU 145肿瘤也没有从抗PSMA缀合的SPION中摄取显著的铁。当从注射的SPION制剂中省略抗PSMA抗体时,观察到类似的非特异性摄取缺乏。PSMA阳性肿瘤摄取的初始铁剂量分数为2.32 ± 0.75%(n = 10); PSMA阴性DU 145肿瘤和不含抗PSMA抗体的SPION摄取为0.16 ± 0.34%(n = 7),PSMA+与PSMA-肿瘤中[Fe]的比值大于15:1(p = 0.01)。抗PSMA缀合SPION的定量[Fe]MRI在体内区分PSMA阳性LNCaP和C4-2和PSMA阴性DU 145人前列腺肿瘤异种移植物。
There is a need for a quantitative MRI method for iron concentration magnetic resonance imaging suitable for measuring the delivery of targeted superparamagnetic iron oxide nanoparticles (SPIONs) to tumors. To apply our newly-developed [Fe]MRI method to the quantitative imaging in both space and time of the iron dynamics of anti-prostate specific membrane antigen (PSMA) conjugated SPIONs within human prostate tumor xenografts in nude mice. Longitudinal 45 Harlan Sprague Dawley athymic nude mice bearing xenografts from PSMA-positive LNCaP, C4-2 and PSMA-negative DU145 tumors from human prostate tumor cell lines. 1.0 Tesla/ T1 and T2 weighted spin echo Image intensity and contrast measurements Student's t-test The SPION diffusion coefficient within tumors was D = 44.8 ± 2.4 × 10-6 mm2/sec. The iron taken up by PSMA-positive LNCaP and C4-2 tumors was proportional to the tail-vein injected dose from 60 nmoles to 1.6 micromoles; injection of 1 micromole of iron in anti-PSMA conjugated SPIONs resulted in a tumor [Fe] of 76 μM. Even at the highest iron dose of 1.6 micromoles, the PSMA-negative DU145 tumors took up no significant iron from the anti-PSMA conjugated SPIONs. A similar lack of non-specific uptake was observed when the antibodies against PSMA were omitted from the injected SPION preparation. The fraction of the initial iron dose that was taken up by PSMA-positive tumors was 2.32 ± 0.75 % (n = 10); uptake by the PSMA-negative DU145 tumors and for SPIONs without anti-PSMA antibodies was 0.16 ± 0.34 % (n = 7) giving a ratio of [Fe] in PSMA+ vs. PSMA- tumors greater than 15:1 (p = 0.01). Quantitative [Fe]MRI of anti-PSMA conjugated SPIONs discriminated between PSMA-positive LNCaP and C4-2 and PSMA-negative DU145 human prostate tumor xenografts in vivo.
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