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:
影响因子:
--
通讯作者:
Sillerud LO
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文献类型:
--
作者:
Sillerud LO
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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影响因子:
8
作者:
Sillerud LO
通讯作者:
Sillerud LO
影响因子:
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发表时间:
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