An ultrasound‐responsive dual‐modal US/T1‐MRI contrast agent for potential diagnosis of prostate cancer

Background

Interest in an ultrasound‐mediated delivery system for effective T₁‐MRI of prostate cancer without adverse effects has steadily increased.

Purpose

To develop an ultrasound‐responsive dual‐modal ultrasound (US)/T₁‐MRI contrast agent for efficient diagnosis of prostate cancer cells overexpressing prostate‐specific membrane antigen (PSMA) and assess their potential.

Study Type

In vitro.

Subjects

Two prostate cancer cell lines.

Field Strength/Sequence

Each study group underwent 3.0T MRI under a TR 400 msec, TE 10 msec, a 240 × 240 matrix, a flip angle 90°, a slice thickness 3 mm, NSA with 4, bandwidth 115 Hz/pixel, and an FOV of 120 × 120 mm.

Assessment

Microscopes, quantitative and qualitative analyzing instruments, and clinical devices were used for assessing this novel contrast agent and its diagnosis effects.

Statistical Tests

We used linear regression analyses to determine the longitudinal relaxivity (r ₁) values of our US/T₁‐MRI contrast agent and gadobutrol.

Results

Microbubble+Fe³⁺melanin nanoparticle+peptides (MB+Fe³⁺MNPPs) had a good US contrast effect, like a commercial US agent. The differences of US intensities between them was below 5%. The r ₁ values of MB+Fe³⁺MNPPs and gadobutrol were 4.5 and 3.7 s^‐1/mM, respectively. More than hundreds of Fe³⁺MNPPs were located in prostate cancer cells treated with MB+Fe³⁺MNPPs and US stimulus, but the number of Fe³⁺MNPPs was below dozens in the other prostate cancer cells expressing less PSMA. The former cells with MB+Fe³⁺MNPPs and US stimulus only showed the highest T₁‐MRI signal because of synergy effects of the peptides targeting the cells and US stimulus for delivery of Fe³⁺MNPPs to the cells. No cytotoxicity of MB+Fe³⁺MNPPs was confirmed by using a WST assay. Viability of the cells with the complexes was above 90%.

Data Conclusion

We synthesized MB+Fe³⁺MNPPs as a potential US/T₁‐MRI contrast agent. This complex was applicable for diagnosing desired prostate cancer cells.

Level of Evidence: 1

Technical Efficacy: Stage 2

J. Magn. Reson. Imaging 2018;48:1610–1616

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