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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Abstract

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/ T1 and T2 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 mm2/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.

Data Conclusion

Level of Evidence: 1

Data Conclusion

Technical Efficacy: Stage 2

Data Conclusion

J. Magn. Reson. Imaging 2017.

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