Short pulses acoustic cluster therapy (ACT)

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Acoustic cluster therapy (ACT) can be used to improve tumor responses to chemotherapeutic agents. This therapy uses diagnostics ultrasound to stimulate uptake of drugs. This study is designed to test if modified clinical ultrasound transducer will get the same or better improved chemotherapeutic efficacy. PC3 tumor bearing mice will be injected with Abraxane and treated with ACT. At the start of this study, the tumors are 100-150 mm3 and will not have given the mice pain or any other discomfort.

The enhanced Abraxane efficacy from the best practice ultrasound settings from FOTS7372 will be compared with ultrasound settings using a modified clinical transducer. PC3 tumor bearing mice will be treated with chemotherapy and ACT, resulting in a bigger tumor growth reduction compared to chemotherapy alone. Current chemotherapy treatment are not sufficient. Increasing drug dose in tumor by 5-10% could improve the clinical outcome of chemotherapy. Thus enhancing drug delivery to the tumor using ACT would be of great benefit in future patient treatments.
54 mice will undergo 4 chemotherapy and ACT treatments (ones a week for 4 weeks). We are not looking for a maximal tolerated doses but want to improve to outcome of clinical relevant doses. The treatment should not cause serious side effects, but some weight loss and discomfort might be expected.The mice will be given extra tasty food after treament, so they will keep their appetite, keeping weight loss to a minimum. We expect that the tumor become smaller and smaller, hopefully disappear completely for more than 100 after treatment. Monitoring weight and tumor size will be done by normal scale and caliper measurements, respectively, which is done without any anesthesia, it is just gentle handling of animal without any stress.

ACT improves chemo because it affects the tumor vascular. Futhermore, the aim is to improve cancer therapy, thus preclinical experiment in mice is required. To obtain data that can be extrapolated to a clinical situation an intact circulation and solid tumor growing in a living animal is necessary. To limit the number of mice simulation studies were performed. However, it is not possible to mimic the complex vascular system of human tumors in simulations and phantom studies to predict its behavior in patients.