Tzu-Yin Wang, Presenter: Nothing to Disclose

Jung Woo Choe, Abstract Co-Author: Nothing to Disclose

Steven B. Machtaler PhD, Abstract Co-Author: Nothing to Disclose

Rammohan Devulapally, Abstract Co-Author: Nothing to Disclose

Butrus T. Khuri-Yakub PhD, Abstract Co-Author: Nothing to Disclose

Ramasamy Paulmurugan PhD, Abstract Co-Author: Nothing to Disclose

Juergen Karl Willmann MD, Abstract Co-Author: Research Consultant, Bracco Group Research Grant, Siemens AG Research Grant, Bracco Group

Ultrasound(US)-microbubble(MB)-mediated drug delivery is a promising technique for image-guided, targeted cancer therapy. To optimize this technique for clinical translations, we performed a systematic study on effects of various US and MB parameters on cavitation and the corresponding delivery results of an FDA approved drug carrier, poly(D,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) nanoparticles (NPs) into tumors.

Cavitation was induced by exposing lipid shelled, perfluorocarbon encapsulated MBs to 1.8-MHz US pulses. Cavitation was evaluated with passive detection of the inertial cavitation dose (ICD) and active imaging of MB destruction. Effects of peak negative pressure, pulse length, pulse repetition frequency (PRF), MB concentration, and focal scanning strategies, on cavitation were studied in an agar tissue phantom. Preliminary in vivo studies were performed to study the feasibility of delivering PLGA-PEG NPs into hepatocellular tumors in mice.

Passive cavitation detection showed that the ICD increased with pressures increasing from 0.5 to 5MPa, and with PRFs increasing from 10 to 100 Hz (N=6 each). The ICD also increased with increasing MB concentration from 4×106 to 1×108 bubbles/mL, but saturated at higher concentration (N=6 each). No significant effect was found for pulse lengths below 15 cycles. Active cavitation imaging confirmed more MB destruction with increasing pressures. When the pressure exceeded 3MPa, more violent cavitation was observed as flickering bright spots at the focus of US. Compared to single focus treatment, electronic focal steering over a large target volume resulted in more homogeneous treatment (N=4 each). Preliminary in vivo experiments showed successful delivery of PLGA-PEG NPs to a hepatocellular tumor.

The pressure, PRF, MB concentration, and focal scanning strategies, have distinct effects on cavitation, while no significant influence was found for short pulse lengths. Preliminary in vivo results demonstrated the feasibility of delivering PLGA-PEG NPs into tumors for targeted cancer therapy.

This study presents a clinically translatable systematic approach for spatially localized and optimized delivery of large drugs/carriers to target sites based on quantitative measurement of cavitation

Wang, T, Choe, J, Machtaler, S, Devulapally, R, Khuri-Yakub, B, Paulmurugan, R, Willmann, J, Effects of Ultrasound Parameters on Cavitation-assisted Delivery of PLGA-PEG Nanoparticles into Tumors: Phantom Study and Preliminary In Vivo Results.  Radiological Society of North America 2013 Scientific Assembly and Annual Meeting, December 1 - December 6, 2013 ,Chicago IL. http://archive.rsna.org/2013/13029184.html