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Quantitative [Fe]MRI determination of the dynamics of PSMA‐targeted SPIONs discriminates among prostate tumor xenografts based on their PSMA expression
Author(s) -
Sillerud Laurel O.
Publication year - 2018
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.25935
Subject(s) - du145 , lncap , prostate cancer , magnetic resonance imaging , glutamate carboxypeptidase ii , prostate , medicine , cancer research , pathology , chemistry , nuclear medicine , cancer , radiology
Background 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. Purpose 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. Study Type Longitudinal. Animal Model 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. Field Strength/Sequence 1.0 Tesla/ T 1 and T 2 weighted spin echo. Assessment Image intensity and contrast measurements. Statistical Tests Student's t‐test. Results The SPION diffusion coefficient within tumors was D = 44.8 ± 2.4 × 10 −6 mm 2 /s. The iron taken up by PSMA‐positive LNCaP and C4‐2 tumors was proportional to the tail‐vein injected dose from 60 nmol to 1.6 μmol; injection of 1 μmol of iron in anti‐PSMA conjugated SPIONs resulted in a tumor [Fe] of 76 μM. Even at the highest iron dose of 1.6 μmol, the PSMA‐negative DU145 tumors took up no significant iron from the anti‐PSMA conjugated SPIONs. A similar lack of nonspecific 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 + versus PSMA‐ tumors greater than 15:1 ( P = 0.01). Data Conclusion 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. Level of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. J. MAGN. RESON. IMAGING 2018;48:469–481.