Nanoparticle-Enabled Selective Destruction of Prostate Tumor Using MRI-Guided Focal Photothermal Therapy

• Published in: The Prostate Vol. 76; no. 13; pp. 1169 - 1181
• Main Authors: Jin, Cheng S., Overchuk, Marta, Cui, Liyang, Wilson, Brian C., Bristow, Robert G., Chen, Juan, Zheng, Gang
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.09.2016; Wiley Subscription Services, Inc
• Subjects: Animals; Fluorodeoxyglucose F18 - administration & dosage; Hot Temperature - therapeutic use; magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical imaging; Mice; Mice, Nude; Nanoparticles - administration & dosage; NMR; Nuclear magnetic resonance; Phototherapy - methods; porphyrin; porphysome; Prostatic Neoplasms - pathology; Prostatic Neoplasms - therapy; Thermometry - methods; magnetic resonance imaging; porphysome; porphyrin
• ISSN: 0270-4137; 1097-0045; 1097-0045
• DOI: 10.1002/pros.23203

BACKGROUND The Magnetic Resonance Imaging (MRI)‐guided focal laser therapy has shown early promise in Phase 1 trial treating low/intermediate‐risk localized prostate cancer (PCa), but the lack of tumor selectivity and low efficiency of heat generation remain as drawbacks of agent‐free laser therapy. Intrinsic multifunctional porphyrin‐nanoparticles (porphysomes) have been exploited to treat localized PCa by MRI‐guided focal photothermal therapy (PTT) with significantly improved efficiency and tumor selectivity over prior methods of PTT, providing an effective and safe alternative to active surveillance or radical therapy. METHODS The tumor accumulation of porphysomes chelated with copper‐64 was determined and compared with the clinic standard 18F‐FDG in an orthotropic PCa mouse model by positron emission tomography (PET) imaging, providing quantitative assessment for PTT dosimetry. The PTT was conducted with MRI‐guided light delivery and monitored by MR thermometry, mimicking the clinical protocol. The efficacy of treatment and adverse effects to surround tissues were evaluated by histology analysis and tumor growth in survival study via MRI. RESULTS Porphysomes showed superior tumor‐to‐prostate selectivity over 18F‐FDG (6:1 vs. 0.36:1). MR thermometry detected tumor temperature increased to ≥55°C within 2 min (671 nm at 500 mW), but minimal increase in surrounding tissues. Porphysome enabled effective PTT eradication of tumor without damaging adjacent organs in orthotropic PCa mouse model. CONCLUSIONS Porphysome‐enabled MRI‐guided focal PTT could be an effective and safe approach to treat PCa at low risk of progression, thus addressing the significant unmet clinical needs and benefiting an ever‐growing number of patients who may be over‐treated and risk unnecessary side effects from radical therapies. Prostate 76:1169–1181, 2016. © 2016 Wiley Periodicals, Inc.