L Chen*, D Cvetkovic, K Cai, B Wang, X Chen, C Ma, Fox Chase Cancer Center, Philadelphia, PA

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  L Chen

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SU-F-206-6 (Sunday, 7/10/2022) 2:00 PM - 3:00 PM [Eastern Time (GMT-4)]

Room 206

Purpose: Our previous study showed significant tumor growth delay in mice treated with pulsed high intensity focused ultrasound (pHIFU). The purpose of this study is to study the mechanisms of tumor growth delay in pHIFU-treated prostate tumors using light microscopy and immunohistochemical (IHC) staining analysis.

Methods: Prostate cancer cells (LNCaP) were grown orthotopically in 12 nude mice. Tumor-bearing mice were treated using pHIFU with an acoustic power of 8W, pulse width 100msec and 300 pulses in one sonication under MR guidance using a commercial clinical device. Mutiple sonications (from 7 to 13) were used to cover the whole tumor volume (121+ 48mm3) depending on the tumor size. Temperature (<40 degrees centigrade in the focal spot) was monitored during the sonication using MR thermometry. Animals were euthanized at pre-determined time points (n=3 for each time point) after treatment: 0.5, 8 and 24 hours. Three tumor-bearing mice were used as control (without pHIFU). The tumors were processed for H&E and immunohistochemically (IHC) stained for caspase 3, CD31, ki-67 and H2AX.

Results: Light microscopy showed hemorrhages, cell nuclear condensation, loss of cytoplasm, and vacuolization in the tumor cells, presumably due to the acoustic cavitations. IHC staining showed Caspase 3 (cell apoptotic marker) peaked at 0.5 hr; Ki-67 peaked at 8 hr and significantly reduced at 24hs after treatment. H2AX (DNA damage marker) also peaked at 0.5 hr, which is similar to Caspase 3, indicating the cells are involved with apoptotic cell death and DNA damage predominant at 0.5hr. In addition, CD31 staining showed nuclear condensation and loss of cytoplasm in vascular endothelial cells.

Conclusion: These results suggest that the tumor growth delay may be caused by acoustic cavitation, apoptosis, DNA damage as well as compromised blood supply.

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