Ultrasound and Microbubbles Increase the Uptake of Platinum in Murine Orthotopic Pancreatic Tumors
Haram, Karin Margrete; Snipstad, Sofie; Berg, Sigrid; Mjønes, Patricia; Rønne, Elin; Lage Fernandez, Jessica; Mühlenpfordt, Melina; Davies, Catharina de Lange
Peer reviewed, Journal article
Published version
Permanent lenke
https://hdl.handle.net/11250/3109746Utgivelsesdato
2023Metadata
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- Institutt for fysikk [2653]
- Institutt for klinisk og molekylær medisin [3426]
- Publikasjoner fra CRIStin - NTNU [37221]
- Publikasjoner fra Cristin - St. Olavs hospital [1459]
- St. Olavs hospital [2441]
Originalversjon
Ultrasound in Medicine and Biology. 2023, 49 (5), 1275-1287. 10.1016/j.ultrasmedbio.2023.01.014Sammendrag
Objective Currently available cytotoxic treatments have limited effect on pancreatic ductal adenocarcinoma (PDAC) because desmoplastic stroma limits drug delivery. Efforts have been made to overcome these barriers by drug targeting the tumor microenvironment. Results so far are promising, but without clinical impact. Our aim was to investigate whether ultrasound and microbubbles could improve the uptake and therapeutic response of conventional chemotherapy. Methods Orthotopic pancreatic tumors growing in mice were treated with commercially available FOLFIRINOX (fluorouracil, irinotecan, oxaliplatin and calcium folinate) and SonoVue microbubbles combined with focused ultrasound. Tumor uptake of platinum (Pt) was measured by inductively coupled plasma mass spectroscopy (ICP-MS), and tumor volumes were measured by ultrasound imaging. Discussion Uptake of Pt, the active ingredient of oxaliplatin, was significantly increased after ultrasound treatment of orthotopic PDAC tumors. Multiple injections with FOLFIRONOX increased the amount of Pt in tumors. However, the enhanced accumulation did not improve therapeutic response. Increased uptake of Pt confirms that ultrasound and microbubbles have potential in clinical practice with existing drugs. Conclusion The lack of therapeutic response, despite increased uptake in tumor tissue, emphasizes the importance of studying how to overcome stromal barriers.