Sprayable pH-sensitive near-infrared fluorophore for rapid, bright, specific, and safe visualization of human thyroid cancer in orthotopic mouse models.
Sunidhi Jaiswal, Atsushi Yamashita, Sohee Lee, Siamak Amirfakhri, Jinhui Ser, Satoshi Kashiwagi, Grace Lin, Robert M Hoffman, Maged Henary, Hak Soo Choi, Michael Bouvet
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引用次数: 0
Abstract
Background: Surgery is the primary treatment for thyroid cancer. However, incomplete resection of thyroid cancer can result in local, regional, and distant recurrences that are life threatening. We hypothesized that a topically applied, pH-sensitive near-infrared fluorophore in spray form (PH10) could offer rapid labeling of thyroid tumors, enabling better visualizion of the tumor and its margins.
Methods: Cellar uptake inhibition and cytotoxicity studies using PH10 were performed on TPC-1 papillary and TT medullary thyroid cancer cells. Subcutaneous or orthotopic tumors were established by injecting TPC-1 cells in the flanks or thyroid glands of nude mice, respectively, and sprayed with PH10. Fluorescence of the tumor was compared to surrounding tissues. Tumors were harvested for pathologic analysis.
Results: The organic anion transporter peptide mediated uptake of PH10 in TPC-1 and TT cells was determined. PH10 exhibited an IC50 value of 13.18 and 17.28 μM in TPC-1 and TT cells, respectively. Both subcutaneous and orthotopic tumors displayed strong near-infrared fluorescence upon spraying PH10 at a concentration of 10 μM on the tumor sites, within 1 minute, contrasting with surrounding tissues. The effective PH10 dose for tumor visualization was well below the IC50. The average tumor to background ratios were 5.5 (±1.47) for subcutaneous tumors (n = 5) and 9.4 (±2.59) for orthotopic tumors (n = 5). Hematoxylin and eosin staining confirmed the tumor characteristics.
Conclusion: The pH-sensitive near-infrared fluorophore PH10 brightly, rapidly, specifically, and safely labeled thyroid cancer in mouse models by spraying, demonstrating future clinical promise as a useful agent for improved visualization of thyroid cancer.
期刊介绍：
For 66 years, Surgery has published practical, authoritative information about procedures, clinical advances, and major trends shaping general surgery. Each issue features original scientific contributions and clinical reports. Peer-reviewed articles cover topics in oncology, trauma, gastrointestinal, vascular, and transplantation surgery. The journal also publishes papers from the meetings of its sponsoring societies, the Society of University Surgeons, the Central Surgical Association, and the American Association of Endocrine Surgeons.
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