An ultrasound-responsive dual-modal US/T -MRI contrast agent for potential diagnosis of prostate cancer.

Background: Interest in an ultrasound-mediated delivery system for effective T -MRI of prostate cancer without adverse effects has steadily increased.

Purpose: To develop an ultrasound-responsive dual-modal ultrasound (US)/T -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 ) values of our US/T -MRI contrast agent and gadobutrol.

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

Data Conclusion: We synthesized MB+Fe MNPPs as a potential US/T -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.