An ultrasound‐responsive dual‐modal US/T1‐MRI contrast agent for potential diagnosis of prostate cancer. Issue 6 (26th November 2018) - Yoon, Young Il
Abstract : 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+Fe 3+ melanin nanoparticle+peptides (MB+Fe 3+ 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+Fe 3+ MNPPs and gadobutrol were 4.5 and 3.7 s ‐1 /mM, respectively. More than hundreds of Fe 3+ MNPPs were located in prostate cancer cells treated with MB+Fe 3+ MNPPs and US stimulus, but the number of Fe 3+ MNPPs was below dozens in the other prostate cancer cells expressing less PSMA. The former cells with MB+Fe 3+ 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 Fe 3+ MNPPs to the cells. No cytotoxicity of MB+Fe 3+ MNPPs was confirmed by using a WST assay. Viability of the cells with the complexes was above 90%. Data Conclusion: We synthesized MB+Fe 3+ 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