Young Il Yoon1,2, Shin-Woo Ha1,3, Hak Jong Lee1,3,4. 1. Department of Radiology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea. 2. IT·Medical Research Team, Korea Textile Development Institute (KTDI), Daegu, Republic of Korea. 3. IMGT Inc., Gyeonggi-do, Republic of Korea. 4. Department of Nanoconvergence, Graduate School of Convergence Science and Technology, Seoul National University, Gyeonggi-do, Republic of Korea.
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 (r1 ) 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 r1 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.
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 (r1 ) 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 r1 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.